bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-vimentin, anti-TUFM, anti-NAP1L1 and anti-DPYSL2 nanobodies display cytotoxic effect and reduce glioblastoma cell migration
Authors: Zottel Alja , Jovčevska Ivana , Šamec Neja , Mlakar Jernej , Šribar Jernej , Križaj Igor , Skoblar Vidmar Marija , Komel Radovan 
Published: April 2020

Background: Glioblastoma is a particularly common and very aggressive primary brain tumour. One of the main causes of therapy failure is the presence of glioblastoma stem cells that are resistant to chemotherapy and radiotherapy, and that have the potential to form new tumours. This study focuses on validation of eight novel antigens, TRIM28, nucleolin, vimentin, nucleosome assembly protein 1-like 1 (NAP1L1), mitochondrial translation elongation factor (EF-TU) (TUFM), dihydropyrimidinase-related protein 2 (DPYSL2), collapsin response mediator protein 1 (CRMP1) and Aly/REF export factor (ALYREF), as putative glioblastoma targets, using nanobodies. Methods: Expression of these eight antigens was analysed at the cellular level by qPCR, ELISA and immunocytochemistry, and in tissues by immunohistochemistry. The cytotoxic effects of the nanobodies were determined using AlamarBlue and water-soluble tetrazolium tests. Annexin V/propidium iodide tests were used to determine apoptotsis/necrosis of the cells in the presence of the nanobodies. Cell migration assays were performed to determine the effects of the nanobodies on cell migration. Results: NAP1L1 and CRMP1 were significantly overexpressed in glioblastoma stem cells in comparison with astrocytes and glioblastoma cell lines at the mRNA and protein levels. Vimentin, DPYSL2 and ALYREF were overexpressed in glioblastoma cell lines only at the protein level. The functional part of the study examined the cytotoxic effects of the nanobodies on glioblastoma cell lines. Four of the nanobodies were selected in terms of their specificity towards glioblastoma cells and protein overexpression: anti-vimentin (Nb79), anti-NAP1L1 (Nb179), anti-TUFM (Nb225) and anti-DPYSL2 (Nb314). In further experiments to optimise the nanobody treatment schemes, to increase their effects, and to determine their impact on migration of glioblastoma cells, the anti-TUFM nanobody showed large cytotoxic effects on glioblastoma stem cells, while the anti-vimentin, anti-NAP1L1 and anti-DPYSL2 nanobodies were indicated as agents to target mature glioblastoma cells. The anti-vimentin nanobody also had significant effects on migration of mature glioblastoma cells. Conclusion: Nb79 (anti-vimentin), Nb179 (anti-NAP1L1), Nb225 (anti-TUFM) and Nb314 (anti-DPYSL2) nanobodies are indicated for further examination for cell targeting. The anti-TUFM nanobody, Nb225, is particularly potent for inhibition of cell growth after long-term exposure of glioblastoma stem cells, with minor effects seen for astrocytes. The anti-vimentin nanobody represents an agent for inhibition of cell migration.
Older adults’ experiences of using a wearable activity tracker with health professional feedback over a 12-month randomised controlled trial
Authors: Brickwood Katie-Jane , Williams Andrew D , Watson Greig , O’Brien Jane 
Published: April 2020

Objective Wearable activity trackers can help older adults remain physically active. However, knowledge of the user experience during long-term use is scarce. Therefore, this study examined older adults’ experiences with, and perceptions of, wearable activity trackers combined with health professional feedback after a year’s use as part of a randomised controlled trial. Methods Twenty older adults (73.6 ± 5.5 years) who had used a Jawbone UP24 activity tracker for 12 months during a randomised controlled trial were recruited for this study. All participants had at least one chronic condition. Acceptability data relating to activity tracker wear time was combined with focus group data to explore participants experiences of long-term activity tracker use. Data was analysed using thematic analysis. Results The activity tracker was well-accepted with the device worn on an average of 86% of possible days and participants reported an overall positive experience. Four themes were identified: (a) increased sense of awareness of activity levels is related to motivation; (b) the level of engagement with the activity tracker influences the user experience; (c) the role of feedback from a health professional in providing ongoing support; d) the role of habits in supporting long-term behaviour change. Conclusions The use of an activity tracker combined with health professional support can assist older adults to maintain their activity levels over 12 months. Consideration should be given to the previous technology experience of users and the design and accuracy of an activity tracker when recommending their use in a research or clinical setting.
One-Year Mortality Rates Following Fracture of the Femoral Neck Treated With Hip Arthroplasty in an Aging Saudi Population: A Trauma Center Experience
Authors: Al-Mohrej Omar A. , Alshaalan Fawaz N. , Aldakhil Sahar S. , Rahman Wael A. 
Published: April 2020

Introduction: Femoral neck fracture is a common problem in elderly patients, and it is managed with either total hip arthroplasty or hemiarthroplasty with very good outcomes. However, the reported 1-year mortality rate is as high as 33%. Material and Methods: This study was a retrospective cohort study. The electronic patient records were searched for all physiologically old patients with displaced femoral neck fractures that were managed with either hemiarthroplasty or total hip arthroplasty. The primary aim of this study was to estimate morbidity and mortality rates at 30 days and 1 year. The secondary outcome was to determine major complications and factors influencing mortality. Results: From January 2017 to December 2018, a total of 99 patients were included in the study. Of those, 57 were female patients. The mortality rate was 15.2%. The significant predictors of death included the age at the time of surgery, readmission within 30 days of initial admission, acute renal impairment, and the need for preoperative medical intervention. Patients treated with total hip arthroplasty had lower mortality rates than those treated with hemiarthroplasty ( P = .017). Discussion: To the best of our knowledge, this is the first study conducted in Saudi Arabia to report detailed perioperative-related complications and outcomes following neck of femur fractures. The results of our study confirm the persistently high morbidity and mortality associated with this patient group. Conclusion: Efforts should be aimed at optimizing preoperative medical management, which is vital to ensure early identification of medically unfit patients.
Texture and composition of magnetite in the Duotoushan deposit, NW China: implications for ore genesis of Fe–Cu deposits
Authors: Hu Xia , Chen Huayong , Huang Xiaowen , Zhang Weifeng 
Published: April 2020

AbstractThe Duotoushan deposit is an important Fe–Cu deposit in the Aqishan–Yamansu metallogenic belt of eastern Tianshan, NW China. Magnetite occurs in two main habits which are common in many Fe–Cu deposits, i.e. platy (TD1 Mag) and granular magnetite (TD2 Mag) have been identified at Duotoushan. Platy magnetite shows two different zones (bright and dark) based on the observations by scanning electron microscopy. The bright part (TD1-L) is the main part of TD1 magnetite and lacks inclusions. The dark part (TD1-D) is very porous and has abundant tiny silicate inclusions. Granular magnetite is usually anhedral with obvious oscillatory zoning in back-scattered electron images. In general, the dark zones of magnetite are characterised by greater Si, Ca, Al and lesser Fe contents than the bright zones. In situ X-ray diffraction (XRD) analysis shows that the lattice parameter of TD1 magnetite is approximately equal to that of standard magnetite and slightly higher than that of TD2 magnetite, indicating that some cations with ionic radii smaller than those of Fe2+ or Fe3+ entered the magnetite lattice by simple or coupled substitution mechanisms in TD2 magnetite.The results in the present study show that the effects of temperature and $f_{{\rm O}_ 2}$ on platy magnetite are very limited and the changing fluid composition might be the major controlling factor for the formation of Duotoushan platy magnetite. Although the possibility that mushketovite transformed from hematite cannot be excluded entirely, evidence from in situ XRD data, pore-volume ratio calculation and the growth habit of intergrown minerals indicates that platy magnetite (TD1) coexisting with amphibole was more likely to have been precipitated originally from hydrothermal fluid. This was then affected by changes in the fluid composition which consequently led to dissolution of primary magnetite (TD1-L) and re-precipitation of TD1-D magnetite (with abundant porosity and mineral inclusions). Meanwhile, granular magnetite (TD2) with oscillatory zoning, and coexisting with epidote and quartz, was precipitated from fluid with periodic variation in temperature. These oscillatory zones are characterised by bands enriched in Si, Al and Ca alternating with bands depleted in these elements. The present investigation revealed a complex evolutionary process for magnetite formation in the Duotoushan deposit. The importance of combined investigation of texture and compositional characterisation of magnetite for study of the ore genesis and evolution of Fe–Cu deposits is highlighted.
Coagulation factor XII contributes to hemostasis when activated by soil in wounds
Authors: Juang Lih Jiin , Mazinani Nima , Novakowski Stefanie K. , Prowse Emily N. P. , Haulena Martin , Gailani David , Lavkulich Leslie M. , Kastrup Christian J. 
Published: April 2020

Abstract
Bleeding is a common contributor to death and morbidity in animals and provides strong selective pressure for the coagulation system to optimize hemostasis for diverse environments. Although coagulation factor XII (FXII) is activated by nonbiologic surfaces, such as silicates, which leads to blood clotting in vitro, it is unclear whether FXII contributes to hemostasis in vivo. Humans and mice lacking FXII do not appear to bleed more from clean wounds than their counterparts with normal FXII levels. We tested the hypothesis that soil, a silicate-rich material abundant in the environment and wounds of terrestrial mammals, is a normal and potent activator of FXII and coagulation. Blood loss was compared between wild-type (WT) and FXII-knocked out (FXII−/−) mice after soil or exogenous tissue factor was applied to transected tails. The activation of FXII and other components of the coagulation and contact system was assessed with in vitro coagulation and enzyme assays. Soils were analyzed by time-of-flight secondary ionization mass spectrometry and dynamic light scattering. Soil reduced blood loss in WT mice, but not FXII−/− mice. Soil accelerated clotting of blood plasma from humans and mice in a FXII-dependent manner, but not plasma from a cetacean or a bird, which lack FXII. The procoagulant activity of 13 soils strongly correlated with the surface concentration of silicon, but only moderately correlated with the ζ potential. FXII augments coagulation in soil-contaminated wounds of terrestrial mammals, perhaps explaining why this protein has a seemingly minor role in hemostasis in clean wounds.
Environmental fungal sensitisation associates with poorer clinical outcomes in COPD
Authors: Tiew Pei Yee , Ko Fanny Wai San , Pang Sze Lei , Matta Sri Anusha , Sio Yang Yie , Poh Mau Ern , Lau Kenny J.X. , Mac Aogáin Micheál , Jaggi Tavleen Kaur , Ivan Fransiskus Xaverius , Gaultier Nicolas E. , Uchida Akira , Drautz-Moses Daniela I. , Xu Huiying , Koh Mariko Siyue , Hui David Shu Cheong , Tee Augustine , Abisheganaden John Arputhan , Schuster Stephan C. , Chew Fook Tim , Chotirmall Sanjay H. 
Published: April 2020

IntroductionAllergic sensitisation to fungi such asAspergillusare associated to poor clinical outcomes in asthma, bronchiectasis and cystic fibrosis; however, clinical relevance in COPD remains unclear.MethodsPatients with stable COPD (n=446) and nondiseased controls (n=51) were prospectively recruited across three countries (Singapore, Malaysia and Hong Kong) and screened against a comprehensive allergen panel including house dust mites, pollens, cockroach and fungi. For the first time, using a metagenomics approach, we assessed outdoor and indoor environmental allergen exposure in COPD. We identified key fungi in outdoor air and developed specific-IgE assays against the top culturable fungi, linking sensitisation responses to COPD outcomes. Indoor air and surface allergens were prospectively evaluated by metagenomics in the homes of 11 COPD patients and linked to clinical outcome.ResultsHigh frequencies of sensitisation to a broad range of allergens occur in COPD. Fungal sensitisation associates with frequent exacerbations, and unsupervised clustering reveals a “highly sensitised fungal predominant” subgroup demonstrating significant symptomatology, frequent exacerbations and poor lung function. Outdoor and indoor environments serve as important reservoirs of fungal allergen exposure in COPD and promote a sensitisation response to outdoor air fungi. Indoor (home) environments with high fungal allergens associate with greater COPD symptoms and poorer lung function, illustrating the importance of environmental exposures on clinical outcomes in COPD.ConclusionFungal sensitisation is prevalent in COPD and associates with frequent exacerbations representing a potential treatable trait. Outdoor and indoor (home) environments represent a key source of fungal allergen exposure, amenable to intervention, in “sensitised” COPD.
Predictors of catheter-related bladder discomfort after gynaecological surgery
Authors: Li S. Y. , Song L. P. , Ma Y. S. , Lin X. M. 
Published: April 2020

Abstract
Background
Urinary catheterization is universally used during surgery, and the incidence of postoperative catheter-related bladder discomfort (CRBD) is very high during recovery. We conducted this study to identify the incidence and predictors of postoperative CRBD after gynaecological surgery in the post-anesthesia care unit (PACU).

Methods
This was a prospective observational study. Patients undergoing gynaecological surgery under general anesthesia with intra-operative urinary catheterization were enrolled. We collected the clinical data, incidence and severity of CRBD, and postoperative pain for the patients. Predictive factors of CRBD were analysed by univariate and multivariate analysis.

Results
A total of 407 patients were included in this study. The incidence of CRBD after gynaecological surgery was 64.6% (mild CRBD: 22.8%; moderate CRBD: 34.2%; and severe CRBD: 7.6%). Univariate analysis showed that age, type of surgery, type of laparoscopic surgery, additional analgesics, and postoperative pain were influencing factors for CRBD. Based on multivariate logistic regression analysis, age ≥ 50 years, uterus-related laparoscopic surgery, and lack of additional analgesics were independent predictors of moderate or severe CRBD.

Conclusions
This observational study revealed that the incidence of CRBD after gynaecological surgery in PACU was very high. Age ≥ 50 years, uterus-related laparoscopic surgery, and lack of additional analgesics were independent predictors of CRBD.

Trial registration
ChiCTR1800016390. Registered on 30 May 2018.
Ocular biomarkers for cognitive impairment in nonagenarians; a prospective cross-sectional study
Authors: van de Kreeke Jacoba A. , Legdeur Nienke , Badissi Maryam , Nguyen H. Ton , Konijnenberg Elles , Tomassen Jori , ten Kate Mara , den Braber Anouk , Maier Andrea B. , Tan H. Stevie , Verbraak Frank D. , Visser Pieter Jelle 
Published: April 2020

Abstract
Background
Ocular imaging receives much attention as a source of potential biomarkers for dementia. In the present study, we analyze these ocular biomarkers in cognitively impaired and healthy participants in a population aged over 90 years (= nonagenarian), and elucidate the effects of age on these biomarkers.

Methods
For this prospective cross-sectional study, we included individuals from the EMIF-AD 90+ study, consisting of a cognitively healthy (N = 67) and cognitively impaired group (N = 33), and the EMIF-AD PreclinAD study, consisting of cognitively healthy controls aged ≥60 (N = 198). Participants underwent Optical Coherence Tomography (OCT) and fundus photography of both eyes. OCT was used to asses total and individual inner retinal layer thickness in the macular region (Early Treatment Diabetic Retinopathy Study circles) as well as peripapillary retinal nerve fiber layer thickness, fundus images were analyzed with Singapore I Vessel Assessment to obtain 7 retinal vascular parameters. Values for both eyes were averaged. Differences in ocular biomarkers between the 2 nonagenarian groups were analyzed using linear regression, differences between the individual nonagenarian groups and controls were analyzed using generalized estimating equations.

Results
Ocular biomarkers did not differ between the healthy and cognitively impaired nonagenarian groups. 19 out of 22 ocular biomarkers assessed in this study differed between either nonagenarian group and the younger controls.

Conclusion
The ocular biomarkers assessed in this study were not associated with cognitive impairment in nonagenarians, making their use as a screening tool for dementing disorders in this group limited. However, ocular biomarkers were significantly associated with chronological age, which were very similar to those ascribed to occur in Alzheimer’s Disease.
Creating value with eHealth: identification of the value proposition with key stakeholders for the resilience navigator app
Authors: Lentferink Aniek , Polstra Louis , D’Souza Austin , Oldenhuis Hilbrand , Velthuijsen Hugo , van Gemert-Pijnen Lisette 
Published: April 2020

Abstract
Background
For a stress-management app to be persuasive and impactful, designers and developers should obtain a clear perspective of the value proposition according to key stakeholders before development. However, this is often not the case. In order to increase the chance of creating an impact by means of the Resilience Navigator app, this study aims to identify key stakeholders and work with them to gain an in-depth understanding of the value proposition of this stress-management app.

Methods
The approach used in this study builds on the approaches taken by Van Limburg et al. and Van Woezik et al. An initial list of stakeholders was identified by means of a literature scan. Stakeholders on this initial list took an online survey to identify key stakeholders with a ranking system. Semi-structured interviews were conducted with a subset of key stakeholders to identify the value proposition using the value proposition canvas as a framework for data collection. Finally, the value proposition was validated by key stakeholders during focus groups.

Results
The key stakeholders identified included employees, employers, participation councils within organisations, HR advisors, product owners, company doctors, and business analysts. The interviews produced a list of approximately one hundred values from which fifteen core values were distilled. One example is to take into account time constraints experienced by users during stress periods. In general, the Resilience Navigator app’s main goal is to increase awareness of personal stress levels and causes of stress. In addition, the sub-goal is to increase skills for effective stress management. The focus groups validated the idea that the most important values were reflected in the value proposition and had been appropriately translated into design elements, according to key stakeholders.

Conclusions
A thorough, bottom-up identification and validation of the value proposition for the Resilience Navigator app was obtained, reflecting key stakeholders’ varying ideas on this piece of eHealth technology. The results will facilitate the continued development of the Resilience Navigator app from the value specification phase to the design phase. In the design phase, the remaining assumptions regarding the app’s value proposition should be tested using rapid prototyping.
The cerebrovascular and neurological impact of chronic smoking on post-traumatic brain injury outcome and recovery: an in vivo study
Authors: Sivandzade Farzane , Alqahtani Faleh , Sifat Ali , Cucullo Luca 
Published: April 2020

AbstractBackgroundTraumatic brain injury (TBI) is among the most prevalent causes of cerebrovascular and neurological damage worldwide. To this end, tobacco smoke (TS) has been shown to promote vascular inflammation, neurovascular impairments, and risk of cerebrovascular and neurological disorders through oxidative stress (OS) stimuli targeting the blood-brain barrier (BBB) endothelium among others. It has been recently suggested that premorbid conditions such as TS may exacerbate post-TBI brain damage and impact recovery.MethodsOur study investigated the mechanisms underlying the exacerbation of TBI injury by TS using a weight drop model. For this purpose, male C57BL/6J mice, age range 6–8 weeks, were chronically exposed to premorbid TS for 3 weeks. Test animals were then subjected to TBI by guided vertical head weight drop using a 30 g metal weight free felling from an 80 cm distance before reaching the target. We analyzed the physical activity and body weight of the mice before TBI and 1 h, 24 h, and 72 h post-injury. Finally, mice were sacrificed to collect blood and brain samples for subsequent biochemical and molecular analysis. Western blotting was applied to assess the expression of Nrf2 (a critical antioxidant transcription factor) as well as tight junction proteins associated with BBB integrity including ZO-1, Occludin, and Claudin-5 from brain tissues homogenates. Levels of NF-kB (a pro-inflammatory transcript factor which antagonizes Nrf2 activity) and pro-inflammatory cytokines IL-6, IL-10, and TNF-α were assessed in blood samples.ResultsOur data revealed that premorbid TS promoted significantly increased inflammation and loss of BBB integrity in TBI when compared to TS-Free test mice. Additionally, mice chronically exposed to TS before TBI experienced a more significant weight loss, behavioral and motor activity deficiency, and slower post-TBI recovery when compared to TS-free TBI mice.ConclusionThe effects of premorbid TS appear consequential to the abrogation of physiological antioxidative and anti-inflammatory response to TBI leading to worsening impairments of the BBB, OS damage, and inflammation. These factors are also likely responsible for the retardation of post-traumatic recovery observed in these animals.