bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maintaining my employment: Learning from people living and working with mental illness
Authors: Jarman Victoria , Hancock Nicola , Scanlan Justin Newton 
Published: April 2016

Introduction Engagement in occupation, including employment, is central to mental health recovery. However, evidence demonstrates that people living with mental illness struggle to maintain their employment. The aim of this qualitative study was to gain a rich understanding of the experiences of people living with mental illness who have managed to maintain their employment, and specifically, the strategies they actively choose and use to stay in work. Method Semi-structured interviews explored the perspectives of 10 people living with mental illness who were successfully maintaining their employment. Data were analysed using constant comparative analysis. Results Participants described maintaining employment through a conscious and active process of using individualised combinations of specific strategies within the broader categories of: identifying and connecting with helpful people; looking after all of me; having a job that fits with who I am; staying motivated; positive reflection and re-framing; and choosing and using strategies in the workplace. Conclusion Occupational therapists might better support long-term employment outcomes for people living with mental illness by adopting a more recovery-oriented approach, facilitating people to actively identify, choose and use their own strategies to maintain employment.
Cognitive functions over the course of 1 year in multiple sclerosis patients treated with disease modifying therapies
Authors: Utz Kathrin S. , Lee De-Hyung , Lämmer Alexandra , Waschbisch Anne , Linker Ralf A. , Schenk Thomas 
Published: April 2016

Objectives: Disease-modifying therapies (DMTs) are applied to delay or prevent disease progression in multiple sclerosis (MS). While this has mostly been proven for physical symptoms, available studies regarding long-term effects of DMTs on cognitive functions are rare and sometimes inconsistent due to methodological shortcomings. Particularly in the case of fingolimod, comprehensive data on cognitive functions are not yet available. Therefore, we set out to reliably assess cognitive functions in patients with relapsing–remitting MS (RRMS) treated with DMTs over 1 year. Methods: Cognitive functions were assessed with eight tests at three timepoints: baseline, 6-month follow up and 12-month follow up. First, we investigated whether the stability of cognitive functions (i.e. not falling below the 5% cut-off in more than one test) over 1 year in RRMS patients ( n = 41) corresponds to the stability in healthy individuals ( n = 40) of a previous study. Second, we compared the percentage of declined and improved patients in the different tests. Third, we compared patients treated with fingolimod ( n = 22) with patients treated with natalizumab ( n = 11) with regard to cognitive stability. Fourth, based on the patient data, the Reliable Change Index was applied to compute cut-offs for reliable cognitive change. Results: Approximately 75% of RRMS patients treated with DMTs remained stable over the course of 1 year. The Paced Auditory Serial Addition Test (PASAT) and the Spatial Recall Test (SPART), produced improvements in 12.5% and 30.6%, respectively, probably due to practice effects. Patients treated with fingolimod did not differ from patients treated with natalizumab with regard to cognitive stability. Conclusions: Cognitive functions remain relatively stable under DMT treatment over 1 year, irrespective of the type of medication. Furthermore, the tests PASAT and SPART should be interpreted cautiously in studies examining performance changes over time. The provided RCI norms may help clinicians to determine whether a difference in two measurements observed in a RRMS patient is reliable.
CRTC1 gene is differentially methylated in the human hippocampus in Alzheimer’s disease
Authors: Mendioroz Maite , Celarain Naiara , Altuna Miren , Sánchez-Ruiz de Gordoa Javier , Zelaya María Victoria , Roldán Miren , Rubio Idoya , Larumbe Rosa , Erro María Elena , Méndez Iván , Echávarri Carmen 
Published: April 2016

Abstract
Background
CRTC1 (CREB regulated transcription coactivator 1) gene plays a role in synaptic plasticity, learning and long-term memory formation in the hippocampus. Recently, CRTC1 has been shown to be downregulated in Alzheimer’s disease (AD). Nevertheless, the mechanisms underlying CRTC1 dysregulation in AD remain unclear.

Methods
To understand better the epigenetic mechanisms regulating CRTC1 expression that may be altered in AD, we profiled DNA methylation at CpG site resolution by bisulfite cloning sequencing in two promoter regions (referred to as Prom1 and Prom2) of the CRTC1 gene in human hippocampus from controls and AD cases. Next, we correlated DNA methylation levels with AD-related pathology, i.e., β-amyloid and phosphorylated-tau (p-tau) burden and also measured CRTC1 mRNA levels by RT-qPCR.

Results
Methylation levels were lower in AD cases as compared to controls within both promoter regions (Prom1: 0.95 % vs. 5 %, p-value < 0.01 and Prom2: 2.80 % vs. 17.80 %, p-value < 0.001). Interestingly, CRTC1 methylation levels inversely correlated with AD-related neuropathological changes, particularly with p-tau deposition (rSpearman = -0.903, p < 0.001). Moreover, a 1.54-fold decrease in CRTC1 mRNA levels was observed in hippocampus of AD cases compared to controls (p < 0.05) supporting the notion that CRTC1 is downregulated in the AD hippocampus.

Conclusions
DNA methylation levels within two distinct promoter regions of the CRTC1 gene were decreased in human hippocampus affected by AD compared with controls and methylation within Prom1 showed a strong inverse correlation with p-tau deposition. Further studies are guaranteed to elucidate the precise role that CRTC1 methylation plays in AD pathophysiology.
LL-37 stimulates the functions of adipose-derived stromal/stem cells via early growth response 1 and the MAPK pathway
Authors: Yang Yoolhee , Choi Hyunju , Seon Mira , Cho Daeho , Bang Sa Ik 
Published: April 2016

Abstract
Background
LL-37 is a naturally occurring antimicrobial peptide found in the wound bed and assists wound repair. No published study has characterized the role of LL-37 in the function(s) of human mesenchymal stem cells (MSCs). This study investigated the functions of adipose-derived stromal/stem cells (ASCs) activated by LL-37 by performing both in vitro assays with cultured cells and in vivo assays with C57BL/6 mice with hair loss.

Methods
Human ASCs were isolated from healthy donors with written informed consent. To examine the effects of LL-37 on ASC function, cell proliferation and migration were measured by a cell counting kit (CCK-8) and a Transwell migration assay. Early growth response 1 (EGR1) mRNA expression was determined by microarray and real-time PCR analyses. The protein levels of EGR1 and regenerative factors were analyzed by specific enzyme-linked immunosorbent assays and western blotting.

Results
LL-37 treatment enhanced the proliferation and migration of human ASCs expressing formyl peptide receptor like-1. Microarray and real-time PCR data showed that EGR1 expression was rapidly and significantly increased by LL-37 treatment. LL-37 treatment also enhanced the production of EGR1. Moreover, small interfering RNA-mediated knockdown of EGR1 inhibited LL-37-enhanced ASC proliferation and migration. Activation of mitogen-activated protein kinases (MAPKs) was essential not only for LL-37-enhanced ASC proliferation and migration but also EGR1 expression; treatment with a specific inhibitor of extracellular signal-regulated kinase, p38, or c-Jun N-terminal kinase blocked the stimulatory effect of LL-37. EGR1 has a strong paracrine capability and can influence angiogenic factors in ASCs; therefore, we evaluated the secretion levels of vascular endothelial growth factor, thymosin beta-4, monocyte chemoattractant protein-1, and stromal cell-derived factor-1. LL-37 treatment increased the secretion of these regenerative factors. Moreover, treatment with the conditioned medium of ASCs pre-activated with LL-37 strongly promoted hair growth in vivo.

Conclusions
These findings show that LL-37 increases EGR1 expression and MAPK activation, and that preconditioning of ASCs with LL-37 has a strong potential to promote hair growth in vivo. This study correlates LL-37 with MSC functions (specifically those of ASCs), including cell expansion, cell migration, and paracrine actions, which may be useful in terms of implantation for tissue regeneration.
Functional imaging for regenerative medicine
Authors: Leahy Martin , Thompson Kerry , Zafar Haroon , Alexandrov Sergey , Foley Mark , O’Flatharta Cathal , Dockery Peter 
Published: April 2016

AbstractIn vivo imaging is a platform technology with the power to put function in its natural structural context. With the drive to translate stem cell therapies into pre-clinical and clinical trials, early selection of the right imaging techniques is paramount to success. There are many instances in regenerative medicine where the biological, biochemical, and biomechanical mechanisms behind the proposed function of stem cell therapies can be elucidated by appropriate imaging. Imaging techniques can be divided according to whether labels are used and as to whether the imaging can be done in vivo.In vivo human imaging places additional restrictions on the imaging tools that can be used. Microscopies and nanoscopies, especially those requiring fluorescent markers, have made an extraordinary impact on discovery at the molecular and cellular level, but due to their very limited ability to focus in the scattering tissues encountered for in vivo applications they are largely confined to superficial imaging applications in research laboratories. Nanoscopy, which has tremendous benefits in resolution, is limited to the near-field (e.g. near-field scanning optical microscope (NSNOM)) or to very high light intensity (e.g. stimulated emission depletion (STED)) or to slow stochastic events (photo-activated localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM)). In all cases, nanoscopy is limited to very superficial applications. Imaging depth may be increased using multiphoton or coherence gating tricks. Scattering dominates the limitation on imaging depth in most tissues and this can be mitigated by the application of optical clearing techniques that can impose mild (e.g. topical application of glycerol) or severe (e.g. CLARITY) changes to the tissue to be imaged. Progression of therapies through to clinical trials requires some thought as to the imaging and sensing modalities that should be used. Smoother progression is facilitated by the use of comparable imaging modalities throughout the discovery and trial phases, giving label-free techniques an advantage wherever they can be used, although this is seldom considered in the early stages. In this paper, we will explore the techniques that have found success in aiding discovery in stem cell therapies and try to predict the likely technologies best suited to translation and future directions.
Selection of Optimal Adjuvant Chemotherapy Regimens for Human Epidermal Growth Factor Receptor 2 (HER2) –Negative and Adjuvant Targeted Therapy for HER2-Positive Breast Cancers: An American Society of Clinical Oncology Guideline Adaptation of the Cancer Care Ontario Clinical Practice Guideline
Authors: Denduluri Neelima , Somerfield Mark R. , Eisen Andrea , Holloway Jamie N. , Hurria Arti , King Tari A. , Lyman Gary H. , Partridge Ann H. , Telli Melinda L. , Trudeau Maureen E. , Wolff Antonio C. 
Published: April 2016

Purpose A Cancer Care Ontario (CCO) guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer including adjuvant targeted therapy for human epidermal growth factor receptor 2 (HER2)–positive breast cancers was identified for adaptation. Methods The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for adapting clinical practice guidelines developed by other organizations. The CCO guideline was reviewed for developmental rigor and content applicability. Results On the basis of the content review of the CCO guideline, the ASCO Panel agreed that, in general, the recommendations were clear and thorough and were based on the most relevant scientific evidence, and they presented options that will be acceptable to patients. However, for some topics addressed in the CCO guideline, the ASCO Panel formulated a set of adapted recommendations on the basis of local context and practice beliefs of the Panel members. Recommendations Decisions regarding adjuvant chemotherapy regimens should take into account baseline recurrence risk, toxicities, likelihood of benefit, and host factors such as comorbidities. In high-risk HER2-negative populations with excellent performance status, anthracycline- and taxane-containing regimens are the standard of care. Docetaxel and cyclophosphamide for four cycles is an acceptable non-anthracycline regimen. In high-risk HER2-positive disease, sequential anthracycline and taxanes administered concurrently with trastuzumab or docetaxel, carboplatin, and trastuzumab for six cycles are recommended. An alternative regimen in a lower-risk, node-negative, HER2-positive population is paclitaxel and trastuzumab once per week for 12 cycles. Trastuzumab should be given for 1 year. Platinum salts should not be routinely administered in the adjuvant triple-negative population until survival efficacy data become available.
Total- and monomethyl-mercury and major ions in coastal California fog water: Results from two years of sampling on land and at sea
Authors: Weiss-Penzias Peter , Coale Kenneth , Heim Wesley , Fernandez Daniel , Oliphant Andrew , Dodge Celeste , Hoskins Dave , Farlin James , Moranville Robert , Olson Alex 
Published: April 2016

Abstract
Marine fog water samples were collected over two summers (2014–2015) with active strand collectors (CASCC) at eight coastal sites from Humboldt to Monterey counties in California, USA, and on four ocean cruises along the California coastline in order to investigate mercury (Hg) cycling at the ocean-atmosphere-land interface. The mean concentration of monomethylmercury (MMHg) in fog water across terrestrial sites for both years was 1.6 ± 1.9 ng L-1 (&lt;0.01–10.4 ng L-1, N = 149), which corresponds to 5.7% (2.0–10.8%) of total Hg (HgT) in fog. Rain water samples from three sites had mean MMHg concentrations of 0.20 ± 0.12 ng L-1 (N = 5) corresponding to 1.4% of HgT. Fog water samples collected at sea had MMHg concentrations of 0.08 ± 0.15 ng L-1 (N = 14) corresponding to 0.4% of HgT. Significantly higher MMHg concentrations in fog were observed at terrestrial sites next to the ocean relative to a site 40 kilometers inland, and the mean difference was 1.6 ng L-1. Using a rate constant for photo-demethylation of MMHg of -0.022 h-1 based on previous demethylation experiments and a coastal-inland fog transport time of 12 hours, a mean difference of only 0.5 ng L-1 of MMHg was predicted between coastal and inland sites, indicating other unknown source and/or sink pathways are important for MMHg in fog. Fog water deposition to a standard passive 1.00 m2 fog collector at six terrestrial sites averaged 0.10 ± 0.07 L m-2 d-1, which was ∼2% of typical rainwater deposition in this area. Mean air-surface fog water fluxes of MMHg and HgT were then calculated to be 34 ± 40 ng m-2 y-1 and 546 ± 581 ng m-2 y-1, respectively. These correspond to 33% and 13% of the rain fluxes, respectively.
Recurrence rate after Delorme’s procedure with simultaneous placement of a Thiersch suture
Authors: Warwick AM , Zimmermann E , Boorman PA , Smart NJ , Gee AS 
Published: April 2016

Introduction Rectal prolapse is a debilitating condition usually affecting elderly women. The management is generally surgical but the optimal operation remains unclear. The recurrence rate after Delorme’s procedure has been found to be similar to that for an abdominal approach. Thiersch sutures have been associated with high rates of complications and recurrence. The aim of this study was to compare the outcomes of Delorme’s procedure with those of a combined Delorme–Thiersch procedure. Methods A retrospective case note review was performed of all patients who underwent Delorme’s procedure for rectal prolapse between 2008 and 2014 in a single centre. Results Sixty-seven patients (63 women) underwent Delorme’s procedure during the study period. The majority (85%) of patients were over 75 years old. Twelve patients had a Thiersch suture placed at the time of the procedure. The median length of stay was 3 days (range: 0–19 days). Postoperative bleeding requiring either transfusion or readmission occurred in five patients (7.5%) and two patients (3.0%) were readmitted with pain. There was no difference in the rate of complications regardless of whether a Thiersch suture had been placed. Recurrence occurred in 8.3% of those who had a Thiersch suture compared with 21.8% of those who did not (p=0.26). There was no difference in the median time to recurrence between the groups. Conclusions There was no increase in complications after placement of a Thiersch suture with Delorme’s procedure. The rate of recurrence could potentially be decreased with this combined technique. Additional studies are required to investigate this further.
The lower and middle Berriasian in Central Tunisia: Integrated ammonite and calpionellid biostratigraphy of the Sidi Kralif Formation
Authors: Maalaoui Kamel , Zargouni Fouad 
Published: April 2016

Abstract
The lower and middle Berriasian sedimentary succession of the Sidi Kralif Formation has been a subject of biostratigraphic study in two key sections in Central Tunisia. Our contribution is an attempt to better define the basal Berriasian interval, between the Berriasella jacobi Zone and the Subthurmannia occitanica Zone. Zonal schemes are established using ammonites and calpionellids, and these permit correlation with other regions of Mediterranean Tethys and beyond. The use of biomarkers afforded by microfossil groups has allowed characterization and direct correlation with four widely accepted calpionellid sub-zones, namely Calpionella alpina, Remaniella, Calpionella elliptica and Tintinopsella longa. The two ammonite zones of Berriasella jacobi and of Subthurmannia occitanica are recognised on the basis of their index species. The parallel ammonite and calpionellid zonations are useful as a tool for correlation and calibration in time and space, thus allowing a better definition of a J/K boundary. The presence of four Berriasian calpionellid bioevents is recognised: (1) the ‘explosion’ of Calpionella alpina, (2) the first occurrence of Remaniella, (3) the first occurrence of Calpionella elliptica and (4) the first occurrence of Tintinopsella longa. The last is here documented as coeval with the presence of Subthurmannia occitanica, which marks the lower/middle Berriasian boundary.
Increased sialylation and reduced fucosylation of exfoliated cervical cells are potential markers of carcinogenesis in the cervix
Authors: Jin Yingji , Kim Seung Cheol , Kim Hyoung Jin , Ju Woong , Kim Yun Hwan , Kim Hong-Jin 
Published: April 2016

Abstract

Background:
The Pap test has been used for over 50 years for primary screening of cervical cancer. There has been no study of glycosylation changes in Pap test samples despite considerable potential of the glycosylation changes as biomarkers for detecting cancerous lesions. In this study, we developed a 96-well platform for enzyme-linked lectin assays (ELLAs) to evaluate glycosylation levels in cervical cells.

Methods:
A total of 117 samples of exfoliated cervical cells (ECCs) from 37 individuals with normal cytology, 20 with cervical intraepithelial neoplasia (CIN) 1, 19 with CIN 2, 26 with CIN 3 and 15 with cervical cancer were analyzed by ELLAs. The wells of 96-well plates were coated with lysates of the cervical cells, and sialylation and fucosylation levels were compared between the groups.

Results:
Sialylation levels increased and fucosylation levels decreased with increasing grade of cervical dysplasia. ELLAs for sialylation [ELLA-Sambucus nigra (SNAs)] and fucosylation [ELLA-Aleuria aurantia lectin (AAL)] discriminated not only CIN 2 and worse (CIN 2+: CIN 2, CIN 3, and cancer) from normal cytology but also CIN 3 and worse (CIN 3+: CIN3 and cancer) from normal cytology. ELLA-SNAs and ELLA-AALs distinguished cancer from normal cytology with a high true-positive rate (TPR) (ELLA-SNAs: 87%; ELLA-AALs: 87%) and low false-positive rate (FPR) (ELLA-SNAs: 19%; ELLA-AALs: 11%).

Conclusions:
The sialylation and fucosylation levels of ECCs as measured by ELLAs have great potential as biomarkers for primary screening of cervical cancer.
Effective quality management practices in routine clinical next-generation sequencing
Authors: de Abreu Francine B. , Peterson Jason D. , Amos Christopher I. , Wells Wendy A. , Tsongalis Gregory J. 
Published: April 2016

AbstractBackground:Molecular technologies have allowed laboratories to detect and establish the profiles of human cancers by identifying a variety of somatic variants. In order to improve personalized patient care, we have established a next-generation sequencing (NGS) test to screen for somatic variants in primary or advanced cancers. In this study, we describe the laboratory quality management program for NGS testing, and also provide an overview of the somatic variants identified in over 1000 patient samples as well as their implications in clinical practice.Methods:Over the past one-and-a-half years, our laboratory received a total of 1028 formalin-fixed, paraffin-embedded (FFPE) tumor tissues, which consisted of non-small-cell lung carcinomas (NSCLCs), colon adenocarcinomas, glioma/glioblastomas, melanomas, breast carcinomas, and other tumor types. During this time period, we implemented a series of quality control (QC) checks that included (1) pre-DNA extraction, (2) DNA quantification, (3) DNA quality, (4) library quantification, (5) post-emulsification PCR, and (6) post-sequencing metrics. At least 10 ng of genomic DNA (gDNA) were used to prepare barcoded libraries using the AmpliSeq CHPv2. Samples were multiplexed and sequenced on Ion Torrent 318 chips using the Ion PGM System. Variants were identified using the Variant Caller Plugin, and annotation and functional predictions were performed using the Golden Helix SVS.Results:A total of 1005 samples passed QC1–3, and following additional library preparation QC checkpoints, 877 samples were sequenced. Samples were classified into two categories: wild-type (127) and positive for somatic variants (750). Somatic variants were classified into clinically actionable (60%) and non-actionable (40%).Conclusions:The use of NGS in routine clinical laboratory practice allowed for the detection of tumor profiles that are essential for the selection of targeted therapies and identification of applicable clinical trials, contributing to the improvement of personalized patient care in oncology.