bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma p-tau181 accurately predicts Alzheimer’s disease pathology at least 8 years prior to post-mortem and improves the clinical characterisation of cognitive decline
Authors: Lantero Rodriguez Juan , Karikari Thomas K. , Suárez-Calvet Marc , Troakes Claire , King Andrew , Emersic Andreja , Aarsland Dag , Hye Abdul , Zetterberg Henrik , Blennow Kaj , Ashton Nicholas J. 
Published: July 2020

AbstractThe neuropathological confirmation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles (NFT) remains the gold standard for a definitive diagnosis of Alzheimer’s disease (AD). Nowadays, the in vivo diagnosis of AD is greatly aided by both cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers. Although highly accurate, their broad implementation is restricted by high cost, limited accessibility and invasiveness. We recently developed a high-performance, ultrasensitive immunoassay for the quantification of tau phosphorylated at threonine-181 (p-tau181) in plasma, which identifies AD pathophysiology with high accuracy. However, it remains unclear whether plasma p-tau181, measured years before the death, can predict the eventual neuropathological confirmation of AD, and successfully discriminates AD from non-AD dementia pathologies. We studied a unique cohort of 115 individuals with longitudinal blood collections with clinical evaluation at 8, 4 and 2 years prior to neuropathological assessment at death. The results demonstrate that plasma p-tau181 associates better with AD neuropathology and Braak staging than a clinical diagnosis 8 years before post-mortem. Moreover, while all patients had a diagnosis of AD dementia during life, plasma p-tau181 proved to discriminate AD from non-AD pathologies with high accuracy (AUC = 97.4%, 95% CI = 94.1–100%) even 8 years before death. Additionally, the longitudinal trajectory of plasma p-tau181 was assessed in all patients. We found that the main increases in plasma p-tau181 occurred between 8 and 4 years prior to death in patients with AD neuropathology and later plateauing. In contrast, non-AD pathologies and controls exhibited minor, albeit significant, increases in p-tau181 up until death. Overall, our study demonstrates that plasma p-tau181 is highly predictive and specific of AD neuropathology years before post-mortem examination. These data add further support for the use of plasma p-tau181 to aid clinical management in primary care and recruitment for clinical trials.
TMEM119 as a specific marker of microglia reaction in traumatic brain injury in postmortem examination
Authors: Bohnert Simone , Seiffert Anja , Trella Stefanie , Bohnert Michael , Distel Luitpold , Ondruschka Benjamin , Monoranu Camelia-Maria 
Published: July 2020

AbstractThe aim of the present study was a refined analysis of neuroinflammation including TMEM119 as a useful microglia-specific marker in forensic assessments of traumatic causes of death, e.g., traumatic brain injury (TBI). Human brain tissue samples were obtained from autopsies and divided into cases with lethal TBI (n = 25) and subdivided into three groups according to their trauma survival time and compared with an age-, gender-, and postmortem interval-matched cohort of sudden cardiovascular fatalities as controls (n = 23). Brain tissue samples next to cortex contusions and surrounding white matter as well as samples of the ipsilateral uninjured brain stem and cerebellum were collected and stained immunohistochemically with antibodies against TMEM119, CD206, and CCR2. We could document the highest number of TMEM119-positive cells in acute TBI death with highly significant differences to the control numbers. CCR2-positive monocytes showed a significantly higher cell count in the cortex samples of TBI cases than in the controls with an increasing number of immunopositive cells over time. The number of CD206-positive M2 microglial cells increased survival time-dependent. After 3 days of survival, the cell number increased significantly in all four regions investigated compared with controls. In sum, we validate a specific and robustly expressed as well as fast reacting microglia marker, TMEM119, which distinguishes microglia from resident and infiltrating macrophages and thus offers a great potential for the estimation of the minimum survival time after TBI.
Comparison of three video head impulse test systems for the diagnosis of bilateral vestibulopathy
Authors: van Dooren T. S. , Starkov D. , Lucieer F. M. P. , Vermorken B. , Janssen A. M. L. , Guinand N. , Pérez-Fornos A. , Van Rompaey V. , Kingma H. , van de Berg R. 
Published: July 2020

Abstract
Introduction
A horizontal vestibulo-ocular reflex gain (VOR gain) of < 0.6, measured by the video head impulse test (VHIT), is one of the diagnostic criteria for bilateral vestibulopathy (BV) according to the Báràny Society. Several VHIT systems are commercially available, each with different techniques of tracking head and eye movements and different methods of gain calculation. This study compared three different VHIT systems in patients diagnosed with BV.

Methods
This study comprised 46 BV patients (diagnosed according to the Báràny criteria), tested with three commercial VHIT systems (Interacoustics, Otometrics and Synapsys) in random order. Main outcome parameter was VOR gain as calculated by the system, and the agreement on BV diagnosis (VOR gain < 0.6) between the VHIT systems. Peak head velocities, the order effect and covert saccades were analysed separately, to determine whether these parameters could have influenced differences in outcome between VHIT systems.

Results
VOR gain in the Synapsys system differed significantly from VOR gain in the other two systems [F(1.256, 33.916) = 35.681, p < 0.000]. The VHIT systems agreed in 83% of the patients on the BV diagnosis. Peak head velocities, the order effect and covert saccades were not likely to have influenced the above mentioned results.

Conclusion
To conclude, using different VHIT systems in the same BV patient can lead to clinically significant differences in VOR gain, when using a cut-off value of 0.6. This might hinder proper diagnosis of BV patients. It would, therefore, be preferred that VHIT systems are standardised regarding eye and head tracking methods, and VOR gain calculation algorithms. Until then, it is advised to not only take the VOR gain in consideration when assessing a VHIT trial, but also look at the raw traces and the compensatory saccades.
A global view of comorbidity in multiple sclerosis: a systematic review with a focus on regional differences, methodology, and clinical implications
Authors: Hauer Larissa , Perneczky Julian , Sellner Johann 
Published: July 2020

AbstractMultiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system which is associated with numerous comorbidities. These include cardiovascular disease, psychiatric and neurologic disturbances, restless leg syndrome, migraine, cancer, autoimmune diseases, and metabolic disorders. Comorbid disease is an important consideration for clinicians treating patients with MS; early presentation of comorbidities can obscure or delay MS diagnosis, as well as significantly impacting the disease course. Improved understanding of comorbidities and their emergence in MS populations is important for improving the quality of life and optimizing treatment for patients. Therefore, we evaluated published studies reporting epidemiologic data on comorbidities and their associated impact on disease progression in patients with MS (PwMS). The prevalence of neurologic, cardiovascular, metabolic, and autoimmune comorbidities was elevated in PwMS in general, and furthermore, this adversely affected a broad range of outcomes. Compared with PwMS, cancer rates in people without MS or the general population were lower, which should prompt further studies into the mechanisms of both diseases. Studies were under-represented in many regions owing to the latitudinal gradient of MS and possible underfunding of studies.
Systematic review and network meta-analyses of third-line treatments for metastatic colorectal cancer
Authors: Walter Thomas , Hawkins Neil S. , Pollock Richard F. , Colaone Fabien , Shergill Suki , Ross Paul J. 
Published: July 2020

Abstract
Background
Limited treatment options are available in chemotherapy-refractory metastatic colorectal cancer (mCRC). The objective was to conduct a systematic literature review (SLR) and exploratory network meta-analysis (NMA) to compare the tolerability and effectiveness of SIRT with Y-90 resin microspheres, regorafenib, TAS-102 (trifluridine/tipiracil), and best supportive care (BSC) as third-line treatment in patients with mCRC.

Methods
An SLR was conducted to identify studies comparing two or more of the treatments and reporting overall survival (OS), progression-free survival, tumor response, or adverse event (AE) incidence. An exploratory NMA was conducted to compare hazard ratios (HRs) for OS using Markov chain Monte Carlo (MCMC) techniques.

Results
Seven studies were identified in the SLR: two double-blind randomized-controlled trials (RCT) for each drug, one open-label RCT, and two non-randomized comparative studies for SIRT. Patient selection criteria differed between studies, with SIRT studies including patients with liver-dominant colorectal metastases. Nausea and vomiting were more frequent with TAS-102 than regorafenib or SIRT; diarrhea was more common with TAS-102 and regorafenib than SIRT. The exploratory NMA suggested that all active treatments improved OS, with HRs of 0.48 (95% CrI 0.30–0.78) for SIRT with Y-90 resin microspheres, 0.63 (0.38–1.03) for TAS-102, and 0.67 (0.40–1.08) for regorafenib each compared to BSC.

Conclusions
Regorafenib, TAS-102 and SIRT using Y-90 resin microspheres are more effective than BSC in third-line treatment of mCRC; however, study heterogeneity made comparisons between active treatments challenging. SIRT is a viable treatment for third-line mCRC and its favorable AE profile should be considered in the therapeutic decision-making process.
Clinal variation in investment into reproduction versus maintenance suggests a ‘pace-of-life’ syndrome in a widespread butterfly
Authors: Günter Franziska , Beaulieu Michaël , Franke Kristin , Toshkova Nia , Fischer Klaus 
Published: July 2020

AbstractExtreme weather events such as heat waves are predicted to increase in the course of anthropogenic climate change. Widespread species are exposed to a variety of environmental conditions throughout their distribution range, often resulting in local adaptation. Consequently, populations from different regions may vary in their capacity to deal with challenging conditions such as thermal stress. In this study, we investigated clinal variation in body size, fecundity, and oxidative markers along a pan-European latitudinal gradient in the green-veined white butterflyPieris napi, and additionally gene expression in German individuals. We exposed butterflies from replicated Italian, German, and Swedish populations to cold, control, or hot temperatures for 24 h. Under hot conditions, molecular chaperones were up-regulated, while oxidative damage remained unaffected and levels of the antioxidant glutathione (GSH) were reduced under cold and hot conditions. Thus, the short-term exposure to heat stress did not substantially affect oxidative balance. Moreover, we found decreased body size and fecundity in cooler compared with warmer regions. Interestingly, oxidative damage was lowest in Swedish animals exhibiting (1) high levels of GSH, (2) low early fecundity, and (3) low larval growth rates. These results suggest that Swedish butterflies have a slower life style and invest more strongly into maintenance, while those from warmer regions show the opposite pattern, which may reflect a ‘pace-of-life’ syndrome.
Transient mantle cooling linked to regional volcanic shut-down and early rifting in the North Atlantic Igneous Province
Authors: Millett J. M. , Hole M. J. , Jolley D. W. , Passey S. R. , Rossetti L. 
Published: July 2020

AbstractThe Paleocene to Early Eocene Faroe Islands Basalt Group (FIBG) comprises a c. 6.5-km-thick lava flow–dominated sequence located within the centre of the North Atlantic Igneous Province (NAIP). The currently defined pre-breakup and syn-breakup sequences of the FIBG are separated by a significant volcanic hiatus, during which time the coal-bearing Prestfjall Formation was deposited. This major volcanic hiatus is identified across large parts of the NAIP and was preceded on the Faroe Islands by a reduction in eruption rate evidenced by an increased number and thickness of inter-lava sedimentary beds between the simple lava flows of the pre-breakup Beinisvørd Formation. High tempo eruptions resumed after this hiatus with the development of the compound lava flow fields of the Malinstindur Formation which reveal limited evidence for inter-lava breaks. In order to investigate this key transition, flow by flow geochemical sampling of a composite c.1.1-km-thick lava flow sequence spanning this transition were collected and analysed. Three chemically distinct groups are defined based on rare earth elements (REEs) and incompatible trace element signatures. Two high-Ti groups (TiO2 > 2 wt%), B2 and B3, dominate the sampled Beinisvørd Formation and display light REE-enriched signatures (La/YbN c. 2.9–5.9) and evidence for garnet in the source melting region (Dy/YbN c. 1.5–1.6). At the very top of the Beinisvørd Formation, a distinct group of lava flows, B1, displaying lower TiO2 for a given MgO wt% (TiO2 c. 1–2 wt%), weakly light REE-enriched profiles (La/YbN c. 1.7–2.4) and a spinel-dominated mantle melting signature (Dy/YbN c. 1.1–1.2) is identified. Sr, Nd and Pb isotopic signatures for the three groups overlap, revealing limited evidence of crustal contamination, and therefore supporting a mantle melting origin for inter-group variations, rather than source composition or contamination. The group B1 lava flows form a unique stratigraphic occurrence on the islands and provide clear evidence for both a reduction in the initial pressure of melting, alongside an increase in the overall degree of partial melting relative to groups B2 and B3. Increased partial melting is interpreted as evidence for the early onset of rifting and lithospheric thinning to the north of the Faroe Islands. The accompanying reduction in initial pressure of melting provides the first petrological evidence that a transient reduction in mantle temperature leads to the province-wide volcanic hiatus. Our study demonstrates an intimate linkage between rifting history and fluctuations in mantle temperature highlighting that any over-arching model for the evolution of the NAIP must take both into equal account.
General surgery and COVID-19: review of practical recommendations in the first pandemic phase
Authors: Bresadola Vittorio , Biddau Carlo , Puggioni Alessandro , Tel Alessandro , Robiony Massimo , Hodgkinson Jonathan , Leo Cosimo Alex 
Published: July 2020

Abstract
Background
In March, 2020, the World Health Organization declared COVID-19 a pandemic. The absence of previous knowledge of COVID-19 has made decision-making difficult for all in health care, including surgical departments. We reviewed the management recommendations for surgical activity and changes to surgical practice, identifying concordances and discrepancies, based on the literature published in the early phase of the pandemic.

Method
We searched the electronic datasets, PubMed Database, Google, and Google Scholar, using the keywords “SARS-CoV-2”, “COVID-19”, “surgery”, “recommendations”, “guideline”, and “triage”. The search was limited to the first 2 months after the pandemic began and was closed on May 6, 2020.

Results
Twenty papers were included in the analysis and their recommendations are divided into the following categories: 1. general aspects, such as maintaining the safety of health personnel and indications for surgery. 2. The preoperative phase, with recommendations about activating different care pathways for COVID-19 positive patients. 3. The operative phase, with recommendations about activating safety measures for aerosol-generating procedures. 4. The postoperative phase, with recommendations for managing operating theatres and patient transfers.

Conclusion
The recommendations proposed in the revised documents are considered good practices aimed at keeping patients and healthcare professionals safe. However, these recommendations must be contextualized in each individual hospital.
Psychosocial factors promoting resilience during the menopausal transition
Authors: Süss Hannah , Willi Jasmine , Grub Jessica , Ehlert Ulrike 
Published: July 2020

AbstractDespite significant biological, psychological, and social challenges in the perimenopause, most women report an overall positive well-being and appear to be resilient to potentially negative effects of this life phase. The objective of this study was to detect psychosocial variables which contribute to resilience in a sample of perimenopausal women. A total of 135 healthy perimenopausal women aged 40–56 years completed a battery of validated psychosocial questionnaires including variables related to resilience, well-being, and mental health. First, using exploratory factor analysis, we examined which of the assessed variables related to resilience can be assigned to a common factor. Second, linear regression analyses were performed to investigate whether a common resilience factor predicts well-being and mental health in the examined sample of women. Optimism (LOT-R-O), emotional stability (BFI-K-N), emotion regulation (ERQ), self-compassion (SCS-D), and self-esteem (RSES) in perimenopausal women can be allocated to a single resilience-associated factor. Regression analyses revealed that this factor is related to higher life satisfaction (SWLS; β = .39, p < .001, adj. R2 = .20), lower perceived stress (PSS-10; β = − .55, p < .001, adj. R2 = .30), lower psychological distress (BSI-18; β = − .49, p < .001, adj. R2 = .22), better general psychological health (GHQ-12; β = − .49, p < .001, adj. R2 = .22), milder menopausal complaints (MRS II; β = − .41, p < .001, adj. R2 = .18), and lower depressive symptoms (ADS-L; β = − .32, p < .001, adj. R2 = .26). The α levels were adjusted for multiple testing. Our findings confirm that several psychosocial variables (optimism, emotional stability, emotion regulation, self-compassion, and self-esteem) can be allocated to one common resilience-associated factor. This resilience factor is strongly related to women’s well-being as well as mental health in perimenopause.
Environmental changes to reduce self-harm on an adolescent inpatient psychiatric ward: an interrupted time series analysis
Authors: Reen Gurpreet K , Bailey Jill , McGuigan Lorna , Bloodworth Natasha , Nawaz Rasanat Fatima , Vincent Charles 
Published: July 2020

AbstractExisting interventions to reduce self-harm in adolescents admitted to psychiatric wards are usually focused on individual psychological treatments. However, the immediate ward environment in which treatment takes place is an important factor in the success of the treatment and can also influence the likelihood of self-harming behaviours. The aim of the current study was to evaluate changes made to a psychiatric ward environment on incidence of self-harm in adolescents. A quasi-experimental interrupted time series study was conducted on one child and adolescent psychiatric ward. An intervention was developed alongside staff and patients to address the high incidence of self-harm on weekday evenings on the ward. The intervention components involved adding a regular twilight shift (3–11 pm) for nursing staff and introducing a structured evening activity programme on the ward. A segmented regression analysis of an interrupted time series found that the rate of self-harm per 100 bed days was already declining at baseline and continued to decline post-intervention, but the rate of decline was not significant (p = 0.415). However, the proportion of patients self-harming was increasing at baseline and significantly reduced post-intervention (p = 0.001), and this reduction was significantly larger in the evenings (p = 0.004) compared to other times of day (p = 0.09). A tailored intervention targeting the psychiatric ward environment helped to reduce the proportion of adolescents self-harming on the ward. An interrupted time series analysis should be considered for future interventions making changes to health systems over time.
Influence of the second layer on geometry and spectral properties of doped two-dimensional hexagonal boron nitride
Authors: Chojecki Michał , Lewandowska Ewa , Korona Tatiana 
Published: July 2020

AbstractInfluence of the additional layer of hexagonal boron nitride (h-BN) on structure, energetics, and electronic spectra of a layer doped with magnesium, silicon, phosphorus, aluminum, or carbon atoms has been examined by theoretical methods. The h-BN layers are modeled as BN clusters of over thirty atoms with the defect in the center. The calculations show that atom positions undergo some modifications in the presence of the second layer, which in several cases lead to significant changes in electronic spectra, like (i) modifications of the character of some states from local excitation to a partial charge transfer; (ii) redshift of the majority of lowest excitations; (iii) absence or appearance of new states in comparison with the monolayers. For instance, a zero-intensity excitation below 4 eV for the carbon atom in place of boron transforms into a dipole-allowed one in the presence of the second layer. A comparison of the interaction energies of doped and undoped clusters shows a strong dependence of the stabilizing of destabilizing effect on the dopant atom, the replaced atom, and in some cases also on the stacking type (AA’ or AB). The stabilization energy per BN pair, calculated for two undoped clusters, is equal to − 31 and − 28 meV for the AA’ and AB stacking, respectively, thus confirming a larger stability of the AA’ stacking for the h-BN case.
Stability studies with tigecycline in bacterial growth medium and impact of stabilizing agents
Authors: Amann Lisa F. , Vicente Emilia Ruda , Rathke Mareike , Broeker Astrid , Riedner Maria , Wicha Sebastian G. 
Published: July 2020

Abstract
Purpose
This study aimed to examine the degradation of tigecycline in Mueller Hinton broth (ca-MHB), as knowledge about bacterial susceptibility is key for therapeutic decisions.

Methods
Antioxidative stabilizers were evaluated on tigecycline stability in a quantitative chromatography assay and tigecycline induced kill against Staphylococcus aureus (ATCC29213) was determined in time kill studies.

Results
Ascorbic acid caused rapid degradation of tigecycline and resulted in loss of antibacterial activity. Tigecycline was stabilized in aged broth by 2% pyruvate and bacterial growth, and tigecycline killing was similar to fresh broth without supplementation, but independent of age.

Conclusion
Our results underline the importance of using freshly prepared ca-MHB or the need for stabilizers for tigecycline susceptibility testing while using aged ca-MHB.
Weighted voting on the IMF Managing Director
Authors: Mayer Alexander , Napel Stefan 
Published: July 2020

AbstractExecutive Directors of the International Monetary Fund elect the Fund’s Managing Director from a shortlist of three candidates; financial quotas of IMF members define the respective numbers of votes. The implied a priori distribution of success (preference satisfaction) is compared across different electoral procedures. The USA’s Executive Director can expect to come closer to its top preference under plurality rule than for pairwise majority comparisons or plurality with a runoff; opposite applies to everybody else. Differences of US success between voting rules dominate the within-rule differences between most other Directors, and much of the latest reform of quotas.