bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sphere-forming cells from peripheral cornea demonstrate the ability to repopulate the ocular surface
Authors: Mathan Jeremy John , Ismail Salim , McGhee Jennifer Jane , McGhee Charles Ninian John , Sherwin Trevor 
Published: June 2016

Abstract
Background
The limbus forms the outer rim of the cornea at the corneoscleral junction and harbours a population of stem cells for corneal maintenance. Injuries to the limbus, through disease or accidents such as chemical injuries or burns, may lead to significant visual impairment due to depletion of the native stem cells of the tissue.

Methods
Sphere-forming cells were isolated from peripheral cornea for potential use as transplantable elements for limbal stem cell repopulation and limbal reconstruction. Immunocytochemistry, live cell imaging and quantitative PCR were used to characterize spheres and elucidate activity post implantation into human cadaveric corneal tissue.

Results
Spheres stained positively for stem cell markers ∆NP63α, ABCG2 and ABCB5 as well as the basal limbal marker and putative niche marker, notch 1. In addition, spheres also stained positively for markers of corneal cells, vimentin, keratin 3, keratocan and laminin, indicating a heterogeneous mix of stromal and epithelial-origin cells. Upon implantation into decellularized corneoscleral tissue, 3D, polarized and radially orientated cell migration with cell proliferation was observed. Cells migrated out from the spheres and repopulated the entire corneal surface over 14 days. Post-implantation analysis revealed qualitative evidence of stem, stromal and epithelial cell markers while quantitative PCR showed a quantitative reduction in keratocan and laminin expression indicative of an enhanced progenitor cell response. Proliferation, quantified by PCNA expression, significantly increased at 4 days subsequently followed by a decrease at day 7 post implantation.

Conclusion
These observations suggest great promise for the potential of peripheral corneal spheres as transplantable units for corneal repair, targeting ocular surface regeneration and stem cell repopulation.
Regenerative medicine in China: demands, capacity, and regulation
Authors: Cheng Biao , Lu Shuliang , Fu Xiaobing 
Published: June 2016

Abstract
Regenerative medicine (RM) is an emerging interdisciplinary field of research. Its clinical application focuses on the repair, replacement, and regeneration of cells, tissues, and organs by approaches including cell reprogramming, stem cell transplantation, tissue engineering, activating factors, and clone treatment. RM has become a hot point of research in China and other countries. China’s main and local governments have attached great importance to RM and given strong support in relevant policies and funding. About 3.5 billion RMB has been invested in this field. Since 1999, China has established about 30 RM centers and cooperates with many advanced countries in RM research and benefits from their cooperation. However, China needs to develop standards, regulations, and management practices suitable for the healthy development of RM. In this review, we focus on its great demand, capacity, and relative regulations.
Rethinking funding priorities in mental health research
Authors: Lewis-Fernández Roberto , Rotheram-Borus Mary Jane , Betts Virginia Trotter , Greenman Lisa , Essock Susan M. , Escobar Javier I. , Barch Deanna , Hogan Michael F. , Areán Patricia A. , Druss Benjamin G. , DiClemente Ralph J. , McGlashan Thomas H. , Jeste Dilip V. , Proctor Enola K. , Ruiz Pedro , Rush A. John , Canino Glorisa J. , Bell Carl C. , Henry Renata , Iversen Portia 
Published: June 2016

SummaryMental health research funding priorities in high-income countries must balance longer-term investment in identifying neurobiological mechanisms of disease with shorter-term funding of novel prevention and treatment strategies to alleviate the current burden of mental illness. Prioritising one area of science over others risks reduced returns on the entire scientific portfolio.
End-of-life care in a psychiatric hospital
Authors: Waterman Lauren Z. , Denton David , Minton Ollie 
Published: June 2016

SummarySince the Liverpool Care Pathway has been withdrawn in the UK, clinicians supporting the palliative needs of patients have faced further challenges, particularly for patients with dementia who are unable to go to a hospice owing to challenging behaviours. It is becoming more important for different services to provide long-term palliative care for patients with dementia. Mental health trusts should construct end-of-life care policies and train staff members accordingly. Through collaborative working, dying patients may be kept where they are best suited. We present the case study of a patient who received end-of-life care at a psychiatric hospital in the UK. We aim to demonstrate how effective end-of-life care might be provided in a psychiatric hospital, in accordance with recent new palliative care guidelines, and highlight potential barriers.
Mind how you cross the gap! Outcomes for young people who failed to make the transition from child to adult services: the TRACK study
Authors: Islam Zoebia , Ford Tamsin , Kramer Tami , Paul Moli , Parsons Helen , Harley Katherine , Weaver Tim , McLaren Susan , Singh Swaran P. 
Published: June 2016

Aims and methodThe Transitions of Care from Child and Adolescent Mental Health Services to Adult Mental Health Services (TRACK) study was a multistage, multicentre study of adolescents' transitions between child and adult mental health services undertaken in England. We conducted a secondary analysis of the TRACK study data to investigate healthcare provision for young people (n = 64) with ongoing mental health needs, who were not transferred from child and adolescent mental health services (CAMHS) to adult mental health services mental health services (AMHS).ResultsThe most common outcomes were discharge to a general practitioner (GP; n =29) and ongoing care with CAMHS (n = 13), with little indication of use of third-sector organisations. Most of these young people had emotional/neurotic disorders (n = 31, 48.4%) and neurodevelopmental disorders (n = 15, 23.4%).Clinical implicationsGPs and CAMHS are left with the responsibility for the continuing care of young people for whom no adult mental health service could be identified. GPs may not be able to offer the skilled ongoing care that these young people need. Equally, the inability to move them decreases the capacity of CAMHS to respond to new referrals and may leave some young people with only minimal support.
Community treatment orders in the UK 5 years on: a repeat national survey of psychiatrists
Authors: DeRidder Ritz , Molodynski Andrew , Manning Catherine , McCusker Pearse , Rugkåsa Jorun 
Published: June 2016

Aims and methodCommunity treatment orders (CTOs) are increasingly embedded into UK practice and their use continues to rise. However, they remain highly controversial. We surveyed psychiatrists to establish their experiences and current opinions of using CTOs and to compare findings with our previous survey conducted in 2010.ResultsThe opinions of psychiatrists in the UK have not changed since 2010 in spite of recent evidence questioning the effectiveness of CTOs. Clinical factors (the need for engagement and treatment adherence, and the achievement of adherence and improved insight) remain the most important considerations in initiating and discharging a CTO.Clinical implicationsGiven the accumulating evidence from research and clinical practice that CTOs do not improve outcomes, it is concerning that psychiatrists' opinions have not altered in response, particularly given the implications for patient care.
Little evidence for community treatment orders – a battle fought with heavy weapons
Authors: Heun Reinhard , Dave Subodh , Rowlands Paul 
Published: June 2016

SummaryThis editorial discusses the pros and cons of community treatment orders (CTOs) from the perspective of community general adult psychiatry. There is little scientific evidence supporting the application of CTOs. Preconditions of a CTO to work are likely to be met by few patients. The time for the application of a CTO may be better spent for patient-centred care until there is sufficient new and robust evidence that identifies the patients that might profit.
Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline
Authors: Khorana Alok A. , Mangu Pamela B. , Berlin Jordan , Engebretson Anitra , Hong Theodore S. , Maitra Anirban , Mohile Supriya G. , Mumber Matthew , Schulick Richard , Shapiro Marc , Urba Susan , Zeh Herbert J. , Katz Matthew H.G. 
Published: June 2016

Purpose To provide evidence-based recommendations to oncologists and others on potentially curative therapy for patients with localized pancreatic cancer. Methods ASCO convened a panel of medical oncology, radiation oncology, surgical oncology, palliative care, and advocacy experts and conducted a systematic review of literature from January 2002 to June 2015. Outcomes included overall survival, disease-free survival, progression-free survival, and adverse events. Results Nine randomized controlled trials met the systematic review criteria. Recommendations A multiphase computed tomography scan of the abdomen and pelvis or magnetic resonance imaging should be performed for all patients to assess the anatomic relationships of the primary tumor and for the presence of intra-abdominal metastases. Baseline performance status, comorbidity profile, and goals of care should be evaluated and established. Primary surgical resection is recommended for all patients who have no metastases, appropriate performance and comorbidity profiles, and no radiographic interface between primary tumor and mesenteric vasculature. Preoperative therapy is recommended for patients who meet specific characteristics. All patients with resected pancreatic cancer who did not receive preoperative therapy should be offered 6 months of adjuvant chemotherapy in the absence of contraindications. Adjuvant chemoradiation may be offered to patients who did not receive preoperative therapy with microscopically positive margins (R1) after resection and/or who had node-positive disease after completion of 4 to 6 months of systemic adjuvant chemotherapy. Patients should have a full assessment of symptoms, psychological status, and social supports and should receive palliative care early. Patients who have completed treatment and have no evidence of disease should be monitored. Additional information is available at www.asco.org/guidelines/PCPC and www.asco.org/guidelineswiki .
Locally Advanced, Unresectable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline
Authors: Balaban Edward P. , Mangu Pamela B. , Khorana Alok A. , Shah Manish A. , Mukherjee Somnath , Crane Christopher H. , Javle Milind M. , Eads Jennifer R. , Allen Peter , Ko Andrew H. , Engebretson Anitra , Herman Joseph M. , Strickler John H. , Benson Al B. , Urba Susan , Yee Nelson S. 
Published: June 2016

Purpose To provide evidence-based recommendations to oncologists and others for treatment of patients with locally advanced, unresectable pancreatic cancer. Methods American Society of Clinical Oncology convened an Expert Panel of medical oncology, radiation oncology, surgical oncology, gastroenterology, palliative care, and advocacy experts and conducted a systematic review of the literature from January 2002 to June 2015. Outcomes included overall survival, disease-free survival, progression-free survival, and adverse events. Results Twenty-six randomized controlled trials met the systematic review criteria. Recommendations A multiphase computed tomography scan of the chest, abdomen, and pelvis should be performed. Baseline performance status and comorbidity profile should be evaluated. The goals of care, patient preferences, psychological status, support systems, and symptoms should guide decisions for treatments. A palliative care referral should occur at first visit. Initial systemic chemotherapy (6 months) with a combination regimen is recommended for most patients (for some patients radiation therapy may be offered up front) with Eastern Cooperative Oncology Group performance status 0 or 1 and a favorable comorbidity profile. There is no clear evidence to support one regimen over another. The gemcitabine-based combinations and treatments recommended in the metastatic setting (eg, fluorouracil, leucovorin, irinotecan, and oxaliplatin and gemcitabine plus nanoparticle albumin-bound paclitaxel) have not been evaluated in randomized controlled trials involving locally advanced, unresectable pancreatic cancer. If there is local disease progression after induction chemotherapy, without metastasis, then radiation therapy or stereotactic body radiotherapy may be offered also with an Eastern Cooperative Oncology Group performance status ≤ 2 and an adequate comorbidity profile. If there is stable disease after 6 months of induction chemotherapy but unacceptable toxicities, radiation therapy may be offered as an alternative. Patients with disease progression should be offered treatment per the ASCO Metastatic Pancreatic Cancer Treatment Guideline. Follow-up visits every 3 to 4 months are recommended. Additional information is available at www.asco.org/guidelines/LAPC and www.asco.org/guidelines/MetPC and www.asco.org/guidelineswiki .
HES factors regulate specific aspects of chondrogenesis and chondrocyte hypertrophy during cartilage development
Authors: Rutkowski Timothy P. , Kohn Anat , Sharma Deepika , Ren Yinshi , Mirando Anthony J. , Hilton Matthew J. 
Published: June 2016

ABSTRACT
RBPjκ-dependent Notch signaling regulates multiple processes during cartilage development, including chondrogenesis, chondrocyte hypertrophy and cartilage matrix catabolism. Select members of the HES- and HEY-families of transcription factors are recognized Notch signaling targets that mediate specific aspects of Notch function during development. However, whether particular HES and HEY factors play any role(s) in the processes during cartilage development is unknown. Here, for the first time, we have developed unique in vivo genetic models and in vitro approaches demonstrating that the RBPjκ-dependent Notch targets HES1 and HES5 suppress chondrogenesis and promote the onset of chondrocyte hypertrophy. HES1 and HES5 might have some overlapping function in these processes, although only HES5 directly regulates Sox9 transcription to coordinate cartilage development. HEY1 and HEYL play no discernable role in regulating chondrogenesis or chondrocyte hypertrophy, whereas none of the HES or HEY factors appear to mediate Notch regulation of cartilage matrix catabolism. This work identifies important candidates that might function as downstream mediators of Notch signaling both during normal skeletal development and in Notch-related skeletal disorders.
Regional variability in diving physiology and behavior in a widely distributed air-breathing marine predator, the South American sea lionOtaria byronia
Authors: Hückstädt Luis A. , Tift Michael S. , Riet-Sapriza Federico , Franco-Trecu Valentina , Baylis Alastair M. M. , Orben Rachael A. , Arnould John P. Y. , Sepulveda Maritza , Santos Macarena , Burns Jennifer M. , Costa Daniel P. 
Published: June 2016

Our understanding of how air-breathing marine predators cope with environmental variability is limited by our inadequate knowledge of their ecological and physiological parameters. Due to their wide distribution along both coasts of the sub-continent, South American sea lions (Otaria byronia) provide a valuable opportunity to study the behavioral and physiological plasticity of a marine predator in different environments. We measured the oxygen stores and diving behavior of South American sea lions throughout most of its range, allowing us to demonstrate that diving ability and behavior vary across its range. We found no significant differences in mass-specific blood volumes of sea lions among field sites and a negative relationship between mass-specific oxygen storage and size, which suggests that exposure to different habitats and geographical locations better explains oxygen storage capacities and diving capability in South American sea lions than body size alone. The largest animals in our study (individuals from Uruguay) were the most shallow and short duration divers, and had the lowest mass-specific total body oxygen stores, while the deepest and longest duration divers (individuals from Southern Chile) had significantly larger mass-specific oxygen stores, despite being much smaller animals.Our study suggests that the physiology of air-breathing diving predators is not fixed, but that it can be adjusted, to a certain extent, depending on the ecological setting and or habitat. These adjustments can be thought of as a “training effect” as the animal continues to push its physiological capacity through greater hypoxic exposure, its breath holding capacity increases.
Monoclonal antibodies against muscle actin isoforms: epitope identification and analysis of isoform expression by immunoblot and immunostaining in normal and regenerating skeletal muscle
Authors: Chaponnier Christine , Gabbiani Giulio 
Published: June 2016

Higher vertebrates (mammals and birds) express six different highly conserved actin isoforms that can be classified in three subgroups: 1) sarcomeric actins, α-skeletal (α-SKA) and α-cardiac (α-CAA), 2) smooth muscle actins (SMAs), α-SMA and γ-SMA, and 3) cytoplasmic actins (CYAs), β-CYA and γ-CYA. The variations among isoactins, in each subgroup, are due to 3-4 amino acid differences located in their acetylated N-decapeptide sequence. The first monoclonal antibody (mAb) against an actin isoform (α-SMA) was produced and characterized in our laboratory in 1986 (Skalli et al., 1986) . We have further obtained mAbs against the 5 other isoforms. In this report, we focus on the mAbs anti-α-SKA and anti-α-CAA obtained after immunization of mice with the respective acetylated N-terminal decapeptides using the Repetitive Immunizations at Multiple Sites Strategy (RIMMS). In addition to the identification of their epitope by immunoblotting, we describe the expression of the 2 sarcomeric actins in mature skeletal muscle and during muscle repair after micro-lesions. In particular, we analyze the expression of α-CAA, α-SKA and α-SMA by co-immunostaining in a time course frame during the muscle repair process. Our results indicate that a restricted myocyte population expresses α-CAA and suggest a high capacity of self-regeneration in muscle cells. These antibodies may represent a helpful tool for the follow-up of muscle regeneration and pathological changes.
Decision-making in the treatment of adult spinal deformity
Authors: Acaroglu Emre ,   European Spine Study Group
Published: June 2016

Adult spinal deformity (ASD) is a very diverse condition that affects the quality of life of the involved individuals deeply. There is an ongoing discussion as to whether treatment should be surgical (which is potentially dangerous) or non-surgical. In addition to a systematic review of literature on the surgical treatment of ASD with special emphasis on complications, a decision-analysis was performed using the patient information within a European multi-centric database of ASD. The probabilities of improvement and complications as well as associated disease burden (utility) were calculated at the baseline and at first-year follow-up. Decision-analysis suggests that the chances of clinical improvement are significantly higher with surgical treatment. Though surgical treatment is significantly more prone to complications, the likelihood of improvement remains higher than that offered by non-surgical treatment. Surgical treatment of ASD appears to be associated with a higher likelihood of clinical improvement. Future work needs to focus on refining the criteria for appropriate patient selection and decreasing the incidence of complications.Cite this article: Acaroglu E, European Spine Study Group. Decision-making in the treatment of adult spinal deformity. EFORT Open Rev 2016;1:167-176. DOI: 10.1302/2058-5241.1.000013.
Chronic osteomyelitis: what the surgeon needs to know
Authors: Panteli Michalis , Giannoudis Peter V. 
Published: June 2016

Chronic osteomyelitis represents a progressive inflammatory process caused by pathogens, resulting in bone destruction and sequestrum formation. It may present with periods of quiescence of variable duration, whereas its occurrence, type, severity and prognosis is multifactorial. The ‘gold standard’ for the diagnosis of chronic osteomyelitis is the presence of positive bone cultures and histopathologic examination of the bone. Its management remains challenging to the treating physician, with a multidisciplinary approach involving radiologists, microbiologists with expertise in infectious diseases, orthopaedic surgeons and plastic surgeons. Treatment should be tailored to each patient according the severity and duration of symptoms, as well as to the clinical and radiological response to treatment. A combined antimicrobial and surgical treatment should be considered in all cases, including appropriate dead space management and subsequent reconstruction. Relapse can occur, even following an apparently successful treatment, which has a major impact on the quality of life of patients and is a substantial financial burden to any healthcare system. Cite this article EFORT Open Rev 2016;1:128–135. DOI: 10.1302/2058-5241.1.000017.
Management of ankle fractures in the elderly
Authors: Rammelt Stefan 
Published: June 2016

The incidence and severity of ankle fractures in elderly patients is increasing steadily. These injuries are challenging to treat and prone to complications. Individual fracture treatment is tailored depending on bone quality, skin conditions, comorbidities, and functional demand of the patient. This article provides a review of current techniques to obtain stable fixation despite poor bone quality. To avoid complications, it is imperative to consider and treat comorbidities such as diabetes and osteoporosis. In the absence of severe systemic comorbidities, the results after open reduction and internal fixation of malleolar fractures in patients above and below 60 years of age are nearly identical, while nonoperative treatment of unstable fractures leads to significantly inferior outcomes. Therefore, the general indications for surgery in elderly patients should not differ from those in younger patients. However, it is essential to detect severe conditions such as Charcot neuro-osteoarthropathy because these require a completely different treatment regime, and standard internal fixation will invariably fail in these patients.Cite this article: Rammelt S. Management of ankle fractures in the elderly. EFORT Open Rev 2016;1:239-246. DOI: 10.1302/2058-5241.1.000023.