bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying unmet needs in long-term stroke care using in-depth assessment and the Post-Stroke Checklist – The Managing Aftercare for Stroke (MAS-I) study
Authors: Hotter Benjamin , Padberg Inken , Liebenau Andrea , Knispel Petra , Heel Sabine , Steube Diethard , Wissel Jörg , Wellwood Ian , Meisel Andreas 
Published: April 2018

Introduction Detailed data on the long-term consequences and treatment of stroke are scarce. We aimed to assess the needs and disease burden of community-dwelling stroke patients and their carers and to compare their treatment to evidence-based guidelines by a stroke neurologist. Methods We invited long-term stroke patients from two previous acute clinical studies ( n = 516) in Berlin, Germany to participate in an observational, cross-sectional study. Participants underwent a comprehensive interview and examination using the Post-Stroke Checklist and validated standard measures of: self-reported needs, quality of life, overall outcome, spasticity, pain, aphasia, cognition, depression, secondary prevention, social needs and caregiver burden. Results Fifty-seven participants (median initial National Institutes of Health Stroke Scale score 10 interquartile range 4–12.75) consented to assessment (median 41 months (interquartile range 36–50) after stroke. Modified Rankin Scale was 2 (median; interquartile range 1–3), EuroQoL index value was 0.81 (median; interquartile range 0.70–1.00). The frequencies for disabilities in the major domains were: spasticity 35%; cognition 61%; depression 20%; medication non-compliance 14%. Spasticity ( p = 0.008) and social needs ( p < 0.001) had the strongest impact on quality of life. The corresponding items in the Post-Stroke Checklist were predictive for low mood ( p < 0.001), impaired cognition ( p = 0.015), social needs ( p = 0.005) and caregiver burden ( p = 0.031). In the comprehensive interview, we identified the following needs: medical review (30%), optimization of pharmacotherapy (18%), outpatient therapy (47%) and social work input (33%). Conclusion These results suggest significant unmet needs and gaps in health and social care in long-term stroke patients. Further research to develop a comprehensive model for managing stroke aftercare is warranted. Clinical Trial Registration: clinicaltrials.gov NCT02320994.
New Technique for Tibiotalar Arthrodesis Using a New Intramedullary Nail Device
Authors: Dabash Sherif , Eisenstein Emmanuel , Abdelgawad Amr 
Published: April 2018

Category: Ankle, Basic Sciences/Biologics Introduction/Purpose: Ankle arthrodesis is performed in a variety of methods.We propose a new technique for tibiotalar arthrodesis using a newly designed intramedullary nail Methods: We proposed the development of an intramedullary device for ankle arthrodesis which spared the subtalar joint using a sinus tarsi approach. Standard saw bones models and computer-assisted modeling and stress analysis were used to develop different nail design geometries and determine the feasibility of insertion. After the final design was constructed, the device was tested on three cadaveric specimens. Results: Four basic nail geometries were developed. The optimal design was composed of two relatively straight segments, each with a different radius of curvature for their respective tibial and talar component. We successfully implemented this design into three cadaveric specimens Conclusion: Our newly designed tibiotalar nail provides a new technique for isolated tibiotalar fusion. It utilizes the advantages of a tibiotalar calcaneal nail and spares the subtalar joint. This design serves as the foundation for future research to include compression options across the tibiotalar joint and eventual transition to clinical practice.
Microvasculature of the Plantar Plate Using Nano-Computed Tomography
Authors: Finney Fred , Scott Jaron , Jepsen Karl , Holmes James , Talusan Paul 
Published: April 2018

Category: Basic Sciences/Biologics, Lesser Toes, Midfoot/Forefoot Introduction/Purpose: Lesser toe plantar plate attenuation or disruption is being increasingly implicated in a variety of very common clinical complaints including metatarsalgia, metatarsal-phalangeal (MTP) joint subluxation and dislocation, hammertoe, crossover toe, etc. A multitude of surgical techniques and devices have been recently developed to facilitate surgical repair of the plantar plate. However, the microvascular anatomy, and therefore the healing potential in large part, has not been addressed. We sought to answer this question by employing a novel technique involving microvascular perfusion and nano-computed tomography (Nano-CT) imaging. Methods: 12 human adult cadaveric lower extremities were amputated distal to the knee. The anterior and posterior tibial arteries were dissected and cannulated proximal to the ankle joint and were perfused with a barium solution. The soft tissues of each foot were then counterstained with phosphomolybdic acid (PMA). The 2nd through 4th toe MTP joints of 12 feet were imaged with Nano-CT at 14-micron resolution. Images were then reconstructed for three-dimensional analysis of the plantar plate microvasculature and calculation of the vascular density along the length of the plantar plate. Results: A microvascular network extends from the surrounding soft tissues at the attachments of the plantar plate on both the metatarsal and proximal phalanx. The mid-substance of the plantar plate appears to be relatively hypovascular. Analysis of the vascular density along the length of the plantar plate demonstrated a consistent trend with increased vascular density at approximately the proximal 30% and distal 20% of the plantar plate (Figure 1). Conclusion: There is a vascular network extending from the surrounding soft tissues into approximately the proximal 30% and the distal 20% of the plantar plate. The hypovascular mid-portion of the plantar plate may play an important role in the underlying patho-anatomy and pathophysiology of this area. We believe our findings likely have significant clinical implications for the reparative potential of this region, and therefore the surgical procedures currently described to accomplish anatomic plantar plate repair.
Prevalence of Deep Vein Thrombosis in Low Risk Patients After Elective Foot and Ankle Surgery
Authors: Sullivan Martin , Kreulen Christopher , Eusebio Ilian Dominiq , Hang Jacqueline , Omari Abdul 
Published: April 2018

Category: Surgical complications Introduction/Purpose: For patients undergoing elective foot or ankle surgery deep vein thrombosis is a recognised risk with morbidity.The literature is often based on a retrospective review of the clinical notes which can be misleading. Surveillance has not been done in the past .Our concern was that the true incidence of DVT may have been underreported and silent DVTs are possible . The study prospectively determines the prevalence of DVT in low risk patients who are non weight bearing for 6 weeks post operatively by having patients undergo clinical detection as well as high resolution ultrasound to determine the presence and extent of deep vein thrombosis (DVT) in the patients operated leg at 2 weeks and 6 weeks after surgery. Methods: 197 patients undergoing elective (i.e. not trauma or achilles ruptures) foot or ankle surgery requiring a period of 6 weeks non weight bearing post operatively were selected for the study over a 2 year period. 83 patients were excluded as being high risk for DVT based on recognised criteria. The remaining 114 patients were included in the study as they were low risk for DVT. All 114 patients were assessed clinically at 2 weeks and 6 weeks post op for the possibility of DVT and this was recorded.The patients were then sent for high resolution U/S scans on the affected leg at 2 and 6 weeks after the surgery . A middle frequency (4-9 MHz) transducer was used for the study, and a lower frequency transducer for obese or swollen legs. The scans were performed at the Vascular Lab at our Institution which performs over 10000 scans annually. Results: 114 patients were in the study. 71 Females and 43 males with average age 52 years . The incidence of DVT was 24.56% (28/114). Of the 28 positive scans, 22 (79%) had no clinical symptoms or signs of DVT. 20/28 (71%) DVTs were diagnosed at the 2 week scan and 15 of these had no symptoms or signs of DVT. 8/28 (29%) patients had clear scans at 2 weeks and positive scans at 6 weeks.In this late onset group 7/8 had no symptoms or signs of a DVT. Only 5% (6/114) patients had symptoms or signs of DVT. The incidence of DVT in the first 2 weeks after surgery was 17.5%. Of the remaining 94 patients, 8.5% developed a DVT after 2 weeks. Conclusion: In low risk patients who are non weight bearing for 6 weeks after elective foot or ankle surgery the prevalence of DVT (25%) is significantly higher than the literature suggests and the majority of patients 79% (22/28) had no symptoms or signs of DVT to assist in the diagnosis. The majority of DVT’s occurred in the first 2 weeks after surgery however 29% of the total number of DVTs occurred between week 3 and week 6 non weight bearing.
Association of polygenic risk score with the risk of chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis
Authors: Kleinstern Geffen , Camp Nicola J. , Goldin Lynn R. , Vachon Celine M. , Vajdic Claire M. , de Sanjose Silvia , Weinberg J. Brice , Benavente Yolanda , Casabonne Delphine , Liebow Mark , Nieters Alexandra , Hjalgrim Henrik , Melbye Mads , Glimelius Bengt , Adami Hans-Olov , Boffetta Paolo , Brennan Paul , Maynadie Marc , McKay James , Cocco Pier Luigi , Shanafelt Tait D. , Call Timothy G. , Norman Aaron D. , Hanson Curtis , Robinson Dennis , Chaffee Kari G. , Brooks-Wilson Angela R. , Monnereau Alain , Clavel Jacqueline , Glenn Martha , Curtin Karen , Conde Lucia , Bracci Paige M. , Morton Lindsay M. , Cozen Wendy , Severson Richard K. , Chanock Stephen J. , Spinelli John J. , Johnston James B. , Rothman Nathaniel , Skibola Christine F. , Leis Jose F. , Kay Neil E. , Smedby Karin E. , Berndt Sonja I. , Cerhan James R. , Caporaso Neil , Slager Susan L. 
Published: April 2018

Key Points
PRS, based on the known CLL loci, predicts CLL risk with high discrimination. This PRS predicts risk of monoclonal B-cell lymphocytosis, a precursor to CLL and a condition that has clinical impact beyond risk for CLL.
Student perceptions of the education environment in a Spanish medical podiatry school
Authors: Palomo‐López Patricia , Becerro‐de‐Bengoa‐Vallejo Ricardo , Calvo‐Lobo César , Tovaruela‐Carrión Natalia , Rodríguez‐Sanz David , Elena Losa‐Iglesias Marta , López‐López Daniel 
Published: April 2018

AbstractBackgroundThe aim of this study was to explore students' perceptions of the educational environment (EE) in a Spanish school of podiatry. Various aspects of EE were compared by academic year in the program.MethodsThis was a cross‐sectional study using a questionnaire to collect perceptions using data from a 2015 survey. Podiatric medical students from Extremadura University participated in this study. EE was assessed with the Dundee Ready Education Environment Measure (DREEM) tool.The DREEM questionnaire covers five domains of student perceptions, including learning, teachers, academic self‐perceptions, atmosphere, and social self‐perceptions.ResultsTwo hundred thirty‐five students participated, resulting in a 90.73% response rate. Participants included similar numbers of students from different years in the program, and most were women. The global EE score was 2.58 out of 4, indicating that students' perceptions were more positive than negative. Although some weaknesses were detected in this school, students viewed the EE positively in all five DREEM domains. Academic year in the program were generally not related to perceptions of EE.ConclusionsPodiatric medical students declared, in general, that the EE was more positive than negative in our school, according to the DREEM questionnaire. However, although the results are on the whole good, some areas need to be revised to make improvements.
Effectiveness of gliclazide MR 60 mg in the management of type 2 diabetes: analyses from the EASYDia trial
Authors: Leiter Lawrence A. , Shestakova Marina V. , Satman Ilhan 
Published: April 2018

Abstract
Background
Although the number of antihyperglycemic agents has expanded significantly, sulfonylureas (in particular gliclazide) remain an important option because of a variety of patient and health system factors. The large, real world, observational, and international EASYDia trial evaluated the effectiveness of gliclazide modified release (MR) 60 mg in individuals with type 2 diabetes with a broad range of diabetes history, body mass index (BMI) and background antihyperglycemic treatment.

Methods
A total of 7170 participants from eight countries, age ≥ 35 years with HbA1c ≥ 7.5% and not treated with insulin, were prescribed 30–120 mg of gliclazide MR 60 mg once daily. HbA1c goals were individualized and dosing uptitrated, as required, over the 6-month long study. In this post hoc subanalysis, efficacy endpoints were analyzed according to stratified baseline HbA1c levels, weight and glucose-lowering regimens. Episodes of hypoglycemia requiring assistance were documented.

Results
At baseline, mean age was 58.9 years, HbA1c 8.8%, BMI 30.1 kg/m2, and diabetes duration 5.1 years. At study end, clinically significant HbA1c improvements (mean change − 1.78%) were noted across all baseline HbA1c strata (> 7.0 to ≤ 8.0%, > 8.0 to ≤ 9.0%, > 9.0 to ≤ 10.0%, and > 10.0%), BMI classifications (18.5 to < 25.0, 25.0 to < 30.0, and ≥ 30.0 kg/m2), and regardless of the original diabetes treatment regimen (P < 0.001 in all cases). In contrast to the subgroups with BMI 25.0–30.0 and ≥ 30.0 kg/m2 that registered weight losses of 0.9 and 2.2 kg, respectively (P < 0.001 vs. baseline weight); the BMI 18.5–24.9 kg/m2 subgroup gained a mean 0.5 kg (P < 0.02 vs. baseline weight). Severe hypoglycemic events were rare (0.06%).

Conclusions
Progressive gliclazide MR 60 mg uptitration was well tolerated and lowered HbA1c across a broad range of HbA1c, BMI and background glucose-lowering therapy. Weight loss was noted when BMI was ≥ 25.0 kg/m2. Individuals with the highest baseline HbA1c and BMI experienced the greatest HbA1c and weight improvements.
Trial registration ISRCTN Registry ISRCTN00943368 on 1st July 2011
Neurodevelopmental assessment of HIV-exposed uninfected and early-treated HIV-infected children: study protocol
Authors: Strehlau Renate , van Aswegen Tamryn , Potterton Joanne 
Published: April 2018

Abstract
Objective
Sub-Saharan Africa has the highest prevalence of children at risk of not achieving their developmental potential, attributable largely to the human immunodeficiency virus (HIV) pandemic coupled with negative environmental factors. Childhood developmental stimulation programmes can mitigate adverse outcomes.

Methods
Neonates testing HIV positive at birth will be initiated on antiretroviral treatment (ART) and receive an age-appropriate stimulation program, updated at 3 monthly intervals through the first year of life. Neurodevelopment at 12 months of age will be assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Outcomes will be compared with HIV-infected and HIV-exposed uninfected children (HEU) not having received the stimulatory intervention. Associations between neurodevelopmental outcomes, environmental factors, and parental stress will be investigated. The study will take place at a single site in Johannesburg, South Africa. This non-randomised controlled intervention study, with a single non-blinded comparative intervention group, aims to investigate whether an early childhood stimulation programme used in conjunction with ART initiated at birth can positively impact neurodevelopmental outcomes at 1 year of age in children infected with HIV.
Trial registration 15 January 2018, Pan African Clinical Trial Registry PACTR201801002967587
Induction of chondrogenesis of human placenta-derived mesenchymal stem cells via heparin-grafted human fibroblast derived matrix
Authors: Noh Yong Kwan , Du Ping , Dos Santos Da Costa Avelino , Park Kwideok 
Published: April 2018

Abstract

Background
Formation of mature and functional articular cartilage is still challenging in cartilage tissue engineering. This study investigates the potential of using heparin-grafted decellularized extracellular matrix (ECM) as a novel growth factor delivery platform towards human placenta-derived mesenchymal stem cells (hPMSCs) chondrogenic differentiation. Human fibroblast-derived extracellular matrix (hFDM) is naturally obtained from in vitro-cultured human lung fibroblasts via a mild decellularization process. hFDM was then conjugated with heparin via N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) chemistry and subject to transforming growth factor (TGF)-β1 immobilization. Once heparin grafted-hFDM (hFDM-hep) and hPMSCs were co-embedded into collagen gel, they were examined for in vitro and in vivo chondrogenesis of hPMSCs for 4 weeks.

Results
We identified heparin moieties on hFDM via toluidine blue O assay and Fourier transform infrared spectroscopy, respectively. We found out that collagen spheroids containing hFDM-hep and TGF-β1 exhibited a sustained release of growth factor for 28 days in vitro. Chondrogenesis of hPMSCs in vitro was supported by accumulated glycosaminoglycan (GAG) content and upregulated chondrogenic specific markers (collagen II, aggrecan, Sox9). Meanwhile, PKH26 - labeled hPMSCs incorporated collagen with either hFDM or hFDM-hep was pre-conditioned in a chondrogenic media for 3 days and subcutaneously implanted in the back of nude mice for 4 weeks. The implanted collagen spheroids containing both hPMSCs and hFDM-hep retained more viable hPMSCs and showed higher level of chondrogenic differentiation, based on immunostaining of collagen type II over collagen alone or Col/hFDM group. In addition, histological examination showed more positive signals of GAG via Safranin-O staining.

Conclusion
TGF-β1-immobilized hFDM-hep can provide an appropriate microenvironment for chondrogenic differentiation of hPMSCs in 3D collagen spheroid.
Recent trends in bioinks for 3D printing
Authors: Gopinathan Janarthanan , Noh Insup 
Published: April 2018

Abstract

Background
The worldwide demand for the organ replacement or tissue regeneration is increasing steadily. The advancements in tissue engineering and regenerative medicine have made it possible to regenerate such damaged organs or tissues into functional organ or tissue with the help of 3D bioprinting. The main component of the 3D bioprinting is the bioink, which is crucial for the development of functional organs or tissue structures. The bioinks used in 3D printing technology require so many properties which are vital and need to be considered during the selection. Combination of different methods and enhancements in properties are required to develop more successful bioinks for the 3D printing of organs or tissue structures.

Main body
This review consists of the recent state-of-art of polymer-based bioinks used in 3D printing for applications in tissue engineering and regenerative medicine. The subsection projects the basic requirements for the selection of successful bioinks for 3D printing and developing 3D tissues or organ structures using combinations of bioinks such as cells, biomedical polymers and biosignals. Different bioink materials and their properties related to the biocompatibility, printability, mechanical properties, which are recently reported for 3D printing are discussed in detail.

Conclusion
Many bioinks formulations have been reported from cell-biomaterials based bioinks to cell-based bioinks such as cell aggregates and tissue spheroids for tissue engineering and regenerative medicine applications. Interestingly, more tunable bioinks, which are biocompatible for live cells, printable and mechanically stable after printing are emerging with the help of functional polymeric biomaterials, their modifications and blending of cells and hydrogels. These approaches show the immense potential of these bioinks to produce more complex tissue/organ structures using 3D bioprinting in the future.
ERBB3-Activating Mutations in Small Bowel Adenocarcinomas
Authors: Cabel Luc , Aparicio Thomas , Bieche Ivan , Svrcek Magali , Zaanan Aziz , Afchain Pauline , Di Fiore Frédéric , Gornet Jean-Marc , Le Corre Delphine , Vacher Sophie , Callens Celine , Bernard Virginie , Laurent-Puig Pierre , Bidard François-Clément 
Published: April 2018

Purpose Functional studies have demonstrated that some mutations of ERBB3, which encodes for human epidermal growth factor receptor (HER) 3, are oncogenic via activation of the ErbB family signaling pathway. Significant clinical activity of anti-HER2 therapies (trastuzumab plus lapatinib combination or afatinib) has been reported in patients with ERBB3-mutated cancers. This study was designed to report the rate of activating ERBB3 mutations in small bowel adenocarcinoma (SBA), a rare tumor type in which we previously reported a high rate (12%) of ERBB2-activating mutations. Materials and Methods DNA from 74 SBAs, previously characterized for ERBB2 mutations and mismatch repair status, was submitted for sequencing of ERBB3 exons 3, 6, 7, 8, and 23. Orthogonal validation by targeted next-generation sequencing was performed. Results Four of 74 SBAs (5.4%) displayed ERBB3-activating mutations, including three p.V104M mutations (c.310 G>A) in exon 3 and one p.E928G mutation (c.2783 A>G) in exon 23. No mutations were detected in exons 6, 7, and 8. ERBB3-activating mutations were associated with microsatellite instability ( P = .002) and the presence of ERBB2-activating mutations ( P = .002). Two SBAs with co-occurrence of ERBB2 and ERBB3 mutations were further analyzed by targeted next-generation sequencing. Mutant allelic frequencies suggested that both mutations were shared by the same clone rather than being harbored by mutually exclusive tumor subclones. Conclusion SBAs display a high rate of ERBB3-activating mutations, which have been shown to be targetable by anti-HER2 therapies. Strikingly, ERBB3 was frequently comutated with ERBB2, suggesting a strong oncogenic addiction of these SBAs to the HER2 pathway.
A peek into cancer-associated fibroblasts: origins, functions and translational impact
Authors: LeBleu Valerie S. , Kalluri Raghu 
Published: April 2018

ABSTRACT
In malignant tumors, cancer cells adapt to grow within their host tissue. As a cancer progresses, an accompanying host stromal response evolves within and around the nascent tumor. Among the host stromal constituents associated with the tumor are cancer-associated fibroblasts, a highly abundant and heterogeneous population of cells of mesenchymal lineage. Although it is known that fibroblasts are present from the tumor's inception to the end-stage metastatic spread, their precise functional role in cancer is not fully understood. It has been suggested that cancer-associated fibroblasts play a key role in modulating the behavior of cancer cells, in part by promoting tumor growth, but evolving data also argue for their antitumor actions. Taken together, this suggests a putative bimodal function for cancer-associated fibroblasts in oncogenesis. As illustrated in this Review and its accompanying poster, cancer-associated fibroblasts are a dynamic component of the tumor microenvironment that orchestrates the interplay between the cancer cells and the host stromal response. Understanding the complexity of the relationship between cancer cells and cancer-associated fibroblasts could offer insights into the regulation of tumor progression and control of cancer.