bluuebunny/crossref_metadata_2025_split huggingface dataset:
From bench to bedside: the past, present and future of therapy for systemic paediatric ALCL, ALK+
Authors: Larose Hugo , Burke G. A. Amos , Lowe Eric J. , Turner Suzanne D. 
Published: January 2019

SummaryAnaplastic large cell lymphoma (ALCL) is a T cell Non‐Hodgkin Lymphoma that mainly presents in paediatric and young adult patients. The majority of cases express a chimeric fusion protein resulting in hyperactivation of anaplastic lymphoma kinase (ALK) as the consequence of a chromosomal translocation. Rarer cases lack expression of ALK fusion proteins and are categorised as ALCL, ALK−. An adapted regimen of an historic chemotherapy backbone is still used to this day, yielding overall survival (OS) of over 90% but with event‐free survival (EFS) at an unacceptable 70%, improving little over the past 30 years. It is clear that continued adaption of current therapies will probably not improve these statistics and, for progress to be made, integration of biology with the design and implementation of future clinical trials is required. Indeed, advances in our understanding of the biology of ALCL are outstripping our ability to clinically translate them; laboratory‐based research has highlighted a plethora of potential therapeutic targets but, with high survival rates combined with a scarcity of funding and patients to implement paediatric trials of novel agents, progress is slow. However, advances must be made to reduce the side‐effects of intensive chemotherapy regimens whilst maintaining, if not improving, OS and EFS.
Perioperative and oncological outcomes of radical prostatectomy for high‐risk prostate cancer in the UK: an analysis of surgeon‐reported data
Authors: Aning Jonathan J. , Reilly Gavin S. , Fowler Sarah , Challacombe Ben , McGrath John S. , Sooriakumaran Prasanna ,   on behalf of the BAUS Section of Oncology
Published: January 2019

ObjectivesTo analyse the perioperative and oncological outcomes of all radical prostatectomies (RPs) performed for high‐risk prostate cancer in the British Association of Urological Surgeons (BAUS) national registry from 2014 to 2015.Patients and MethodsWe identified and analysed outcomes of all RPs performed for high‐risk prostate cancer (clinical stage >T2 and/or biopsy Gleason grade >7 and/or preoperative prostate‐specific antigen level ≥20 ng/mL) in the national registry for 2014 and 2015. Surgeon reporting of data was mandated during this period. Institution and individual surgeon volume–outcome relationships were assessed.ResultsIn total, 3671/13 947 (26.3%) patients underwent RP for high‐risk prostate cancer over the 2‐year period. Robot‐assisted RP was the most prevalent approach (60.7%). In all, 39% of men received an extended pelvic lymph node dissection (LND), but over one‐third (33.8%) had no LND. Minimally invasive techniques were associated with a significantly shorter length of stay. The reported rates of Clavien–Dindo ≥III complications within the dataset were low (2.0%), regardless of surgical modality or surgeon volume. No statistically significant surgeon volume–outcome relationships were identified when surgeon volume was stratified into tertiles.ConclusionRP for high‐risk prostate cancer in the UK appears safe, regardless of modality used or surgeon volume. No clear evidence that surgeon volume impacts on early perioperative outcomes was seen. Quality assurance of the surgeon‐reported BAUS dataset is now required to drive quality improvement in national practice.
A within‐subject clinical trial on the conversion of mandibular two‐implant to three‐implant overdenture: Patient‐centered outcomes and willingness to pay
Authors: Emami Elham , Alesawy Aminah , de Grandmont Pierre , Cerutti‐Kopplin Daiane , Kodama Naoki , Menassa Mélanie , Rompré Pierre , Durand Robert 
Published: January 2019

AbstractObjectivesTo examine the impact of adding a third midline implant with stud attachment to a mandibular two‐implant overdenture on patient‐oriented outcomes.MethodsIn this pre–post design clinical trial, following the standard procedures, mandibular two‐implant overdentures of 17 edentulous individuals (61.9 ± 6.6 years) were converted to three‐implant overdentures by adding a stud attachment to an unloaded midline implant. Patient‐oriented outcomes included patient expectations and satisfaction with implant overdenture as well as willingness to pay the cost of conversion. Data were collected at baseline and at the 6‐week follow‐up using visual analog and binary scales as well as open‐ended questions. Statistical analysis included descriptive statistics, Spearman's correlation, Fisher exact test, Mann–Whitney U test, and the exact sign test.ResultsAfter connecting the third midline implant to the mandibular two‐implant overdenture, there was a statistically significant decrease in the anteroposterior movement (p = 0.005) as evaluated by clinicians. Moreover, study participants reported an increase in perceived stability of the overdenture (95% CI; 0.68–1.00, p = 0.002) and in their ability to speak (95% CI; 0.63–1.00, p = 0.008). The addition of a third implant met the expectations of 94% of patients in regard to lower denture stability, 100% for retention, and 82.4% for comfort. The mandibular three‐implant overdenture increased patient general satisfaction over a short period of time, but this improvement was not statistically significant. About 80% of patients would recommend this type of prosthesis to their peers but only 47% of them would agree to pay a large increase in the cost of treatment compared to a two‐implant overdenture.ConclusionsThe addition of a midline third implant to an existing mandibular two‐implant overdenture resulted in several improved patient‐reported outcomes.
Association study of cell cycle proteins and human papillomavirus in laryngeal cancer in Chinese population
Authors: Cui Lifang , Qu Congling , Liu Honggang 
Published: January 2019

ObjectiveTo investigate the role of human papillomavirus (HPV) in laryngeal squamous cell carcinoma (LSCC) and analyse the relationship between HPV and the expression of cell cycle‐related proteins.DesignThe study consisted of LSCC between 2005 and 2011 in Tongren Hospital. Clinical data such as age, sex, smoking/alcohol consumption, and TNM stage were collected. HPV DNA and cell cycle‐related proteins were assessed in terms of clinical features.SettingSingle‐centre study.ParticipantsA total of 332 LSCC patients were included in the study.Main outcome measuresThe presence of genotype‐specific HPV DNA was evaluated using PCR‐RDB in formalin‐fixed paraffin‐embedded tissues. All samples were also evaluated for p16INK4A, p21WAF1/CIP1, P53, Cyclin D1, and Ki67 immunohistochemical staining by tissue microarray.ResultsHPV DNA was detected in 45 of 332 (13.55%) patients with LSCC, with HPV‐16 being the predominant genotype. The presence of HPV‐16 DNA was significantly associated with basaloid squamous cell carcinoma and cystic lymph node metastasis (P < 0.05). Of the 332 patients, 36 (10.84%) were scored as p16INK4A positivity and they were more likely to be female (P < 0.05). Cyclin D1‐positivity and p21WAF1/CIP1‐positivity were observed in 60.24% (200/332) and 40.66% (135/332), respectively. In 114 cases (34.33%), LSCCs had moderate‐ to ‐strong p53 accumulation, which was correlated with TNM stage (P < 0.05). HPV‐16 DNA was correlated with p16INK4A and manifested a higher Ki‐67 labelling index and p21WAF1/CIP1 expression than HPV‐16‐negative tumours (P < 0.05). No relationship was observed between Cyclin D1or P53 expression and HPV‐16 infection (P > 0.05).ConclusionHPV DNA was detected in 13.55% patients with LSCC, with HPV‐16 being the predominant genotype and it was correlated with p16INK4A and manifested a higher Ki‐67 labelling index and p21WAF1/CIP1 expression than HPV‐16‐negative tumours.
Characteristics of Single Pivotal Trials Supporting Regulatory Approvals of Novel Non‐orphan, Non‐oncology Drugs in the European Union and United States from 2012−2016
Authors: Morant Anne Vinther , Jagalski Vivien , Vestergaard Henrik Tang 
Published: January 2019

For regulatory approval of a new medicine, the gold standard for demonstration of efficacy has traditionally been a minimum of two positive, adequate, and well‐controlled clinical trials. Nevertheless, drugs to treat cancer and rare diseases are usually approved based on a single and often uncontrolled pivotal trial. In contrast, little is known about single pivotal trial approvals for non‐orphan, non‐oncology drugs. Between 2012 and 2016, 23 novel therapeutic drugs were approved by the US Food and Drug Administration (FDA) and/or the European Medicines Agency (EMA) for 27 non‐orphan, non‐oncology indications each based on a single pivotal trial. Although there was considerable variation in the nature and strength of the efficacy evidence supporting these drug approvals, the majority (85%) of the pivotal trials were randomized and controlled. For all superiority trials, the primary outcome was met with a statistical significance of P ≤ 0.005. Most approvals were supported by additional efficacy data from nonpivotal studies.
Estimating Promotion Effects Using Big Data: A Partially Profiled LASSO Model with Endogeneity Correction*
Authors: Sun Luping , Zheng Xiaona , Jin Ying , Jiang Minghua , Wang Hansheng 
Published: January 2019

ABSTRACTRetailers are interested in understanding which price promotions are profitable and which are not. However, simultaneously estimating the promotion effects of a large number of products on retailer sales and profits is technically challenging for both researchers and practitioners. To address this challenge, this study proposes a Partially Profiled Least Absolute Shrinkage and Selection Operator (Partially Profiled LASSO) model, which can estimate ultra‐high‐dimensional regression relationships at a low computational cost and control for the endogeneity of promotion depth. The model can flexibly incorporate the time‐varying promotion effects and the cross‐over effects among the promotions of different products. We conduct an empirical study using data provided by a large retailer over a 5‐month period. Our model efficiently identifies products with promotion effects and the promotion effects are significantly associated with certain promotion, product, and category characteristics. The results also show that our model with cross‐over effects outperforms the benchmark models that are widely used to handle the high‐dimensional predictor matrix (e.g., the standard LASSO and principal component regression methods). This article contributes to the related literature on price promotion and marketing analytics in data‐rich environments, and provides implications for retailers to make more informed promotion strategies.
Evaluation of dental students’ knowledge and patient care towards HIV/AIDS individuals
Authors: Lorosa Adair H. , Pereira Claudia M. , Hussne Renata P. , Silva‐Boghossian Carina M. 
Published: January 2019

AbstractPurposeThe aim was to evaluate the knowledge of the students of dental students regarding patients care towards HIV positive individuals.MethodsTwo hundred and eighty‐three dental students (pre‐clinical, n = 45; clinical, n = 238) answered an electronic questionnaire, approaching biosafety procedures, oral manifestations of AIDS and knowledge of HIV infection. Data were present as an average from findings from students of nine different semesters, grouping them by pre‐clinical (1‐4) and clinical (5‐9) semesters, from two different university campuses. Furthermore, data were analysed using the t test and chi‐square test.ResultsStudents’ mean age was 24 years. Amongst 14 oral manifestations questioned, Kaposi sarcoma, oral candidiasis, necrotizing ulcerative gingivitis and herpes simplex were more associated with HIV. Over 90% of the respondents would be concerned about becoming infected with HIV after a needle stick injury and were willing to be tested for HIV; know that HIV/AIDS patients can contaminate dental care professionals, that needle perforation can transmit HIV, and that medical professionals are more prone to cross‐contamination. Regarding the use of physical barrier, almost all participants use disposable mask, goggles, cap and procedure gloves with all patients; the use of disposable lab coat and two pairs of gloves were the least used with all patients.ConclusionsParticipating students have good knowledge on biosafety in the management of HIV/AIDS patients, as well as on the most commonly associated oral manifestations. However, there is a need for improvement on some topics related to HIV/AIDS, especially regarding less known oral lesions, and HIV diagnostic tests.
Increased intrinsic connectivity for structural atrophy and functional maintenance after acute ischaemic stroke
Authors: Yang Y. , Chen Y. , Chen K. , Wei D. , Li P. , Zeng W. , Pei J. , Mao H. , Jia J. , Zhang Z. 
Published: January 2019

Background and purposeSignificant clinical recovery has commonly been observed in ischaemic stroke patients with irreversible brain structural damage. However, brain mechanisms that help to maintain clinical function remain unclear.MethodsSixty‐two patients with acute ischaemic stroke underwent longitudinal clinical assessments and magnetic resonance scanning. The clinical recovery trajectory was evaluated using a hierarchical linear model and intrinsic connectivity was analysed with a seed‐based approach to examine its changing pattern based on the regional volume changes calculated using voxel‐wise analysis.ResultsIt was observed that clinical outcome measures improved mainly in the short‐term period (baseline versus 3 weeks) and then remained stable. Grey matter volume was reduced significantly in the bilateral caudate over the entire 3‐year long‐term period. Significant intrinsic connectivity increases were observed in the caudate–middle cingulum over the short‐term period and in the caudate–precuneus and caudate–calcarine over the long‐term period. Finally, it was found that increased caudate–calcarine connectivity was associated with reduced right caudate volume, and a positive correlation was found between increased caudate–middle cingulum connectivity and the amount of modified Rankin score changes.ConclusionsThe increased intrinsic connectivity found in this study tends to be a compensatory mechanism for post‐stroke structural damage, associated with clinical recovery. The study helps in understanding the significance of enhanced intrinsic connectivity in post‐stroke long‐term assessment and rehabilitation.
Self‐organizing hair peg‐like structures from dissociated skin progenitor cells: New insights for human hair follicle organoid engineering and Turing patterning in an asymmetric morphogenetic field
Authors: Weber Erin L. , Woolley Thomas E. , Yeh Chao‐Yuan , Ou Kuang‐Ling , Maini Philip K. , Chuong Cheng‐Ming 
Published: January 2019

AbstractHuman skin progenitor cells will form new hair follicles, although at a low efficiency, when injected into nude mouse skin. To better study and improve upon this regenerative process, we developed an in vitro system to analyse the morphogenetic cell behaviour in detail and modulate physical‐chemical parameters to more effectively generate hair primordia. In this three‐dimensional culture, dissociated human neonatal foreskin keratinocytes self‐assembled into a planar epidermal layer while fetal scalp dermal cells coalesced into stripes, then large clusters, and finally small clusters resembling dermal condensations. At sites of dermal clustering, subjacent epidermal cells protruded to form hair peg‐like structures, molecularly resembling hair pegs within the sequence of follicular development. The hair peg‐like structures emerged in a coordinated, formative wave, moving from periphery to centre, suggesting that the droplet culture constitutes a microcosm with an asymmetric morphogenetic field. In vivo, hair follicle populations also form in a progressive wave, implying the summation of local periodic patterning events with an asymmetric global influence. To further understand this global patterning process, we developed a mathematical simulation using Turing activator‐inhibitor principles in an asymmetric morphogenetic field. Together, our culture system provides a suitable platform to (a) analyse the self‐assembly behaviour of hair progenitor cells into periodically arranged hair primordia and (b) identify parameters that impact the formation of hair primordia in an asymmetric morphogenetic field. This understanding will enhance our future ability to successfully engineer human hair follicle organoids.
Access and barriers to oral health care for dependent elderly people living in rest homes
Authors: Gopalakrishnan Anoop , Kahu Ella , Jones Linda , Brunton Paul 
Published: January 2019

AbstractAimTo report New Zealand rest home (rest home is the New Zealand term for residential aged care facilities where dependent, institutionalised, elderly people reside.) managers’ opinions on access and barriers to oral health care for rest home residents.MethodsAn exploratory study using qualitative descriptive methods. Eleven rest home managers in a region of New Zealand were interviewed about admission assessments for new residents, oral health care, availability of dental facilities, staff training in oral hygiene, residents’ nutritional needs and oral hygiene aids.ResultsInterviews with managers indicated that rest homes have no policies for the provision of oral health care and only arrange dental check‐ups or treatment when requested by residents or family. Barriers to accessing care include making appointments, availability of staff and transport particularly for bedridden patients. Staff receive basic oral hygiene training only and face resistance to oral hygiene from some residents. No homes had a dental chair at their premises. All rest homes stocked oral hygiene aids such as toothbrushes and toothpastes. Electric toothbrushes were not generally promoted with cost being a key factor.ConclusionWhile rest home managers were aware of the importance of good oral health, there are barriers to care. Finance is a challenge as dental care is not publicly funded and many residents rely on a limited income. Recommendations include policy changes to better fund oral health, specific oral health training for rest home staff, provision of mobile dental services to rest homes and the inclusion of gerodontology in the dental school curriculum.
Death of chondrocytes in Kashin‐Beck disease: Apoptosis, necrosis or necroptosis?
Authors: Zhang Ying , He Ying , Zhang Dan , Zhang Meng , Wang Mengying , Zhang Ying , Ma Tianyou , Chen Jinghong 
Published: January 2019

SummaryThe purpose of this paper was to investigate chondrocyte distribution and death in the cartilage in Kashin‐Beck disease (KBD). Apoptotic chondrocytes were detected by TUNEL assay. Ultrastructural changes were examined by transmission electron microscope (TEM). Biochemical markers associated with apoptosis (eg, caspase‐3) and necroptosis (eg, RIP3) were investigated by immunohistochemistry. In KBD cartilage chondrocyte death was characterized by paler staining of the cells. Multiple chondral cell clusters surrounded the areas lacking cells in the deep zone. The per cent of TUNEL‐positive and RIP3‐positive chondrocytes were higher in the middle zones of KBD samples; however, there was some positive staining for TUNEL but negative staining for caspase‐3. Immunohistochemistry failed to detect significant differences in caspase‐3 levels in KBD children compared to controls, suggesting that beside apoptosis necroptosis dominates as a cell death mechanism in the middle zone of cartilage from KBD children. To clarify further the presence of chondrocyte necroptosis in KBD, we performed TUNEL, caspase‐3 and RIP3 staining in a rat KBD model which is based upon T‐2 toxin treatment under selenium‐deficient conditions. Apoptosis and necroptosis co‐existed in the middle zone in this rat KBD model. Ultrastructural analysis of chondrocyte from deep cartilage revealed abnormal cells with numerous morphological changes, such as plasma membrane breakdown, generalized swelling of the cytoplasm and loss of identifiable organelles. Chondrocyte death by necrosis in the deep zone of cartilages in KBD may be a result of exposure to T‐2 toxin from bone marrow or bloodstream under selenium‐deficient nutrition status in KBD endemic areas. Chondrocyte death plays a key role in either the initiation or the progression of KBD pathogenesis.
Recent trends for the employment of jumbo squid (Dosidicus gigas) by‐products as a source of bioactive compounds with nutritional, functional and preservative applications: a review
Authors: Ezquerra‐Brauer Josafat Marina , Aubourg Santiago P. 
Published: January 2019

SummaryOnly 50%–60% of total seafood catch is used for human consumption, seafood processing being considered as one of the main sources of by‐products. Among marine species, jumbo squid (JS; Dosidicus gigas) represents the most important squid fishery, showing an increasing economic interest in many countries. As for any other marine species, the regular cleaning, dressing and processing produce high quantities of by‐products (skin, head, fins, viscera, tentacles, unclaimed mantle, etc.) that are rich in many nutrients (proteins, lipids, minerals, vitamins, enzymes, biopolymers, etc.). This review compiles information about extraction and employment of JS by‐products with the aim of enhancing their economic value and reduce environmental drawbacks. A special emphasis is given to the relevance in developing methods susceptible to transform by‐products into useful and profitable products susceptible to be applied in several industries such as food, medicine, agrochemical or pharmaceutical. Future possible trends for widening this profitable use are mentioned.
Effects of germination on tocopherol, secoisolarlciresinol diglucoside, cyanogenic glycosides and antioxidant activities in flaxseed (Linum usitatissimum L.)
Authors: Li Xiang , Li Jingyan , Dong Shan , Li Yufei , Wei Liping , Zhao Caicai , Li Junyi , Liu Xuebo , Wang Yutang 
Published: January 2019

SummaryThe changes in chemical composition and antioxidant activities of brown and golden flaxseeds (Linum usitatissimum L.) during 5‐day germination were investigated. Flaxseeds germinated in a dark and closed incubator at the temperature of 25 °C. With noticeable reduction in fat content, germinated flaxseeds were determined higher percentage of linolenic acid. The total phenolic content and antioxidant activities increased with germination time. The highest amount of secoisolarlciresinol diglucoside (SDG) was found in 2‐day germinated brown and golden flaxseeds, which increased 1.04‐fold and 1.09‐fold, respectively, and germinated flaxseed oil was found rich in SDG. Intriguingly, germination increased the α‐tocopherol content from 0 to 4.58 mg per 100 g and 0 to 7.83 mg per 100 g in brown and golden flaxseeds while γ‐tocopherol decreased. Germination process also reduced the total content of cyanogenic glucosides, the content of linustatin, neolinustatin and lotaustralin decreased significantly, but caused an increase in the content of linamarin. Therefore, germination can be utilised as an effective method to improve the nutritional value of flaxseed.