bluuebunny/crossref_metadata_2025_split huggingface dataset:
Grey zone amyloid burden affects memory function: the SCIENCe project
Authors: Ebenau J. L. , Verfaillie S. C. J. , van den Bosch K. A. , Timmers T. , Wesselman L. M. P. , van Leeuwenstijn M. , Tuncel H. , Golla S. V. S. , Yaqub M. M. , Windhorst A. D. , Prins N. D. , Barkhof F. , Scheltens P. , van der Flier W. M. , van Berckel B. N. M. 
Published: September 2020

Abstract
Purpose
To determine thresholds for amyloid beta pathology and evaluate associations with longitudinal memory performance with the aim to identify a grey zone of early amyloid beta accumulation and investigate its clinical relevance.

Methods
We included 162 cognitively normal participants with subjective cognitive decline from the SCIENCe cohort (64 ± 8 years, 38% F, MMSE 29 ± 1). Each underwent a dynamic [18F] florbetapir PET scan, a T1-weighted MRI scan and longitudinal memory assessments (RAVLT delayed recall, n = 655 examinations). PET scans were visually assessed as amyloid positive/negative. Additionally, we calculated the mean binding potential (BPND) and standardized uptake value ratio (SUVr50–70) for an a priori defined composite region of interest. We determined six amyloid positivity thresholds using various data-driven methods (resulting thresholds: BPND 0.19/0.23/0.29; SUVr 1.28/1.34/1.43). We used Cohen’s kappa to analyse concordance between thresholds and visual assessment. Next, we used quantiles to divide the sample into two to five subgroups of equal numbers (median, tertiles, quartiles, quintiles), and operationalized a grey zone as the range between the thresholds (0.19–0.29 BPND/1.28–1.43 SUVr). We used linear mixed models to determine associations between thresholds and memory slope.

Results
As determined by visual assessment, 24% of 162 individuals were amyloid positive. Concordance with visual assessment was comparable but slightly higher for BPND thresholds (range kappa 0.65–0.70 versus 0.60–0.63). All thresholds predicted memory decline (range beta − 0.29 to − 0.21, all p < 0.05). Analyses in subgroups showed memory slopes gradually became steeper with higher amyloid load (all p for trend < 0.05). Participants with a low amyloid burden benefited from a practice effect (i.e. increase in memory), whilst high amyloid burden was associated with memory decline. Memory slopes of individuals in the grey zone were intermediate.

Conclusion
We provide evidence that not only high but also grey zone amyloid burden subtly impacts memory function. Therefore, in case a binary classification is required, we suggest using a relatively low threshold which includes grey zone amyloid pathology.
Locality of Interatomic Interactions in Self-Consistent Tight Binding Models
Authors: Thomas Jack 
Published: September 2020

AbstractA key starting assumption in many classical interatomic potential models for materials is a site energy decomposition of the potential energy surface into contributions that only depend on a small neighbourhood. Under a natural stability condition, we construct such a spatial decomposition for self-consistent tight binding models, extending recent results for linear tight binding models to the nonlinear setting.
Intravenous paracetamol in comparison with ibuprofen for the treatment of patent ductus arteriosus in preterm infants: a randomized controlled trial
Authors: Dani Carlo , Lista Gianluca , Bianchi Silvia , Mosca Fabio , Schena Federico , Ramenghi Luca , Zecca Enrico , Vento Giovanni , Poggi Chiara , Leonardi Valentina , Minghetti Diego , Rosignoli Maria Teresa , Calisti Fabrizio , Comandini Alessandro , Cattaneo Agnese , Lipone Paola 
Published: September 2020

AbstractOur aim was to assess the efficacy and safety of intravenous (i.v.) paracetamol vs. i.v. ibuprofen for the treatment of hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. This is a multicenter randomized controlled study. Infants with a gestational age of 25+0–31+6 weeks were randomized to receive i.v. paracetamol (15 mg/kg/6 h for 3 days) or i.v. ibuprofen (10-5-5 mg/kg/day). The primary outcome was the closure rate of hsPDA after the first treatment course with paracetamol or ibuprofen. Secondary outcomes included the constriction rate of hsPDA, the re-opening rate, and the need for surgical closure. Fifty-two and 49 infants received paracetamol or ibuprofen, respectively. Paracetamol was less effective in closing hsPDA than ibuprofen (52 vs. 78%; P = 0.026), but the constriction rate of the ductus was similar (81 vs. 90%; P = 0.202), as confirmed by logistic regression analysis. The re-opening rate, the need for surgical closure, and the occurrence of adverse effects were also similar.Conclusions: Intravenous paracetamol was less effective in closing hsPDA than ibuprofen, but due to a similar constriction effect, its use was associated with the same hsPDA outcome. These results can support the use of i.v. paracetamol as a first-choice drug for the treatment of hsPDA.Trial registration:Clinicaltrials.gov: NCT02422966, Date of registration: 04/09/2015; EudraCT no: 2013-003883-30.

What is Known:• The successful closure of patent ductus arteriosus with oral paracetamol has been recently reported in several preterm infants, but only one randomized controlled study investigated the efficacy of intravenous paracetamol.

What is New:• Intravenous paracetamol is less effective in closing hsPDA than ibuprofen, but have a similar constriction effect.• These results can support the use of i.v. paracetamol as a first-choice drug for the treatment of hsPDA.
Results of a randomized trial of treatment modalities in patients with low or early-intermediate risk prostate cancer (PREFERE trial)
Authors: Wiegel Thomas , Albers Peter , Bartkowiak Detlef , Bussar-Maatz Roswitha , Härter Martin , Kristiansen Glen , Martus Peter , Wellek Stefan , Schmidberger Heinz , Grozinger Klaus , Renner Peter , Schneider Fried , Burmester Martin , Stöckle Michael 
Published: September 2020

Abstract
Purpose
The optimal treatment for patients with low to early-intermediate risk prostate cancer (PCa) remains to be defined. The randomized PREFERE trial (DRKS00004405) aimed to assess noninferiority of active surveillance (AS), external-beam radiotherapy (EBRT), or brachytherapy by permanent seed implantation (PSI) vs. radical prostatectomy (RP) for these patients.

Methods
PREFERE was planned to enroll 7600 patients. The primary endpoint was disease specific survival. Patients with PCa stage ≤ cT2a, cN0/X, M0, PSA ≤ 10 ng/ml and Gleason-Score ≤ 3 + 4 at reference pathology were eligible. Patients were allowed to exclude one or two of the four modalities, which yielded eleven combinations for randomization. Sixty-nine German study centers were engaged in PREFERE.

Results
Of 2251 patients prescreened between 2012 and 2016, 459 agreed to participate in PREFERE. Due to this poor accrual, the trial was stopped. In 345 patients reference pathology confirmed inclusion criteria. Sixty-nine men were assigned to RP, 53 to EBRT, 93 to PSI, and 130 to AS. Forty patients changed treatment shortly after randomization, 21 to AS. Forty-eight AS patients with follow-up received radical treatment. Median follow-up was 19 months. Five patients died, none due to PCa; 8 had biochemical progression after radical therapy. Treatment-related acute grade 3 toxicity was reported in 3 RP patients and 2 PSI patients.

Conclusions
In this prematurely closed trial, we observed an unexpected high rate of termination of AS and an increased toxicity related to PSI. Patients hesitated to be randomized in a multi-arm trial. The optimal treatment of low and early-intermediate risk PCa remains unclear.
Influence of Acid Swallows on the Dynamics of the Upper Esophageal Sphincter
Authors: Miller Simone , Ptok Martin , Jungheim Michael 
Published: September 2020

AbstractMechanisms of the upper esophageal sphincter (UES) when exposed to acid are still incompletely understood. The presented work investigated the reaction of the UES to acid exposure during swallowing. Ten healthy individuals swallowed ten 2 ml neutral water boli of pH 7, followed by 10 swallows each of different levels of acidity (pH 1.8, pH 3 and pH 5). Effects were analyzed by high-resolution manometry (HRM) for the primary parameter Restitution Time, as well as Resting Pressures, maximal, minimal pressures and time intervals. Restitution Times measured mean values of 12.67 s (SD ± 7.03 s) for pH 1.8, pH 7 = 8.69 s (SD ± 2.72 s), pH 3 = 7.56 s (SD ± 2.23 s) and pH 5 = 7.29 s (SD ± 2.55 s), showing prolonged Restitution Times in the UES when exposed to strong bolus acidity. This difference was significant towards the neutral bolus, but also to less acidic boli (pH 5: p = 0.006, pH 3: p = 0.009, pH 7: p = 0.038). Considerable differences of mean values were found for Post-Swallow Maximum and Period of Sphincter Activity. Also, Pre-Swallow Maximum values were found to be highest with the strongest acid. Relaxation Times showed a slight trend of prolongation for the highest bolus acidity. Prolonged Restitution Times may represent a reflexive protective mechanism triggered by receptors in the pharyngeal mucosa or the UES preventing regurgitation of acid into the pharynx and larynx, besides representing ongoing attempts of acid clearance. Exposure to high levels of acidity by a swallowed bolus does influence UES functions during swallowing.
Macrophage polarization in peri-implantitis lesions
Authors: Galarraga-Vinueza Maria Elisa , Obreja Karina , Ramanauskaite Ausra , Magini Ricardo , Begic Amira , Sader Robert , Schwarz Frank 
Published: September 2020

Abstract
Objectives
To immunohistochemically characterize and correlate macrophage M1/M2 polarization status with disease severity at peri-implantitis sites.

Materials and methods
A total of twenty patients (n = 20 implants) diagnosed with peri-implantitis (i.e., bleeding on probing with or without suppuration, probing depths ≥ 6 mm, and radiographic marginal bone loss ≥ 3 mm) were included. The severity of peri-implantitis was classified according to established criteria (i.e., slight, moderate, and advanced). Granulation tissue biopsies were obtained during surgical therapy and prepared for immunohistological assessment and macrophage polarization characterization. Macrophages, M1, and M2 phenotypes were identified through immunohistochemical markers (i.e., CD68, CD80, and CD206) and quantified through histomorphometrical analyses.

Results
Macrophages exhibiting a positive CD68 expression occupied a mean proportion of 14.36% (95% CI 11.4–17.2) of the inflammatory connective tissue (ICT) area. Positive M1 (CD80) and M2 (CD206) macrophages occupied a mean value of 7.07% (95% CI 5.9–9.4) and 5.22% (95% CI 3.8–6.6) of the ICT, respectively. The mean M1/M2 ratio was 1.56 (95% CI 1–12–1.9). Advanced peri-implantitis cases expressed a significantly higher M1 (%) when compared with M2 (%) expression. There was a significant correlation between CD68 (%) and M1 (%) expression and probing depth (PD) values.

Conclusion
The present immunohistochemical analysis suggests that macrophages constitute a considerable proportion of the inflammatory cellular composition at peri-implantitis sites, revealing a significant higher expression for M1 inflammatory phenotype at advanced peri-implantitis sites, which could possibly play a critical role in disease progression.

Clinical relevance
Macrophages have critical functions to establish homeostasis and disease. Bacteria might induce oral dysbiosis unbalancing the host’s immunological response and triggering inflammation around dental implants. M1/M2 status could possibly reveal peri-implantitis’ underlying pathogenesis.
Maternal serum Vitamin B12 and offspring attention-deficit/hyperactivity disorder (ADHD)
Authors: Sourander Andre , Silwal Sanju , Upadhyaya Subina , Surcel Heljä-Marja , Hinkka-Yli-Salomäki Susanna , McKeague Ian W. , Cheslack-Postava Keely , Brown Alan S. 
Published: September 2020

AbstractMaternal Vitamin B12 deficiency during pregnancy is associated with offspring neuropsychiatric disorders. Few previous studies examining this association with attention-deficit/hyperactivity disorder (ADHD) report inconsistent findings. The study examines the association between maternal serum Vitamin B12 levels and offsprings’ risk of ADHD. This study is based on the Finnish Prenatal Study of ADHD with a nested case–control design. All the singleton children born in Finland between January 1998 and December 1999 and diagnosed with ADHD were included in the study. A total of 1026 cases were matched with an equal number of controls on sex, date of birth and place of birth. Maternal Vitamin B12 levels were assessed using a chemiluminescence microparticle immunoassay and archived from maternal serum banks, collected during the first and early second trimester of pregnancy. Lower maternal Vitamin B12 levels when analyzed as a continuous variable was not associated with offspring ADHD (aOR 0.97, 95% CI 0.79–1.18, p = 0.75). No significant associations were seen in the lowest quintile of Vitamin B12 levels (aOR 0.96, 95% CI 0.73–1.27, p = 0.80). This is the first study examining maternal sera Vitamin B12 levels during early pregnancy and offspring ADHD. The result suggests that Vitamin B12 deficiency during early pregnancy has specificity for some disorders but not with offspring ADHD.
Hydrocarbon generation from lacustrine shales with retained oil during thermal maturation
Authors: Shao Xin-He , Pang Xiong-Qi , Li Mao-Wen , Li Zhi-Ming , Zhao Yi 
Published: September 2020

AbstractThermal maturation in the shale oil/gas system is inherently complex due to the competitive interplays between hydrocarbon generation and retention processes. To study hydrocarbon generation characteristics from shales within different stages of thermal maturation under the influence of retained oil, we performed Micro-Scale Sealed Vessels (MSSV) pyrolysis on a set of artificially matured lacustrine shale samples from the Shahejie Formation in the Dongpu Depression in Bohai Bay Basin, China. Experimental results show that hydrocarbon yields of shale samples with or without retained oil at various thermal maturities follow different evolution paths. Heavy components (C15+) in samples crack at high temperatures and generally follow a sequence, where they first transform into C6–14 then to C2–5 and C1. Methane accounts for most of the gaseous products at high temperatures in all samples, with different origins. The cracking of C2–5 is the main methane-generating process in samples with retained oil, whereas the source of methane in samples without retained oil is kerogen. In the studied shales, retained oils at early-mature stage retard the transformation of liquid to gaseous hydrocarbon and prompt the cracking of C2–5 to C1 to some extent. TSR reaction related to gypsum in the studied samples is the primary reason that can explain the loss of hydrocarbon yields, especially at high temperatures. In addition, transformation of volatile hydrocarbons to gas and coke also accounts for the loss of generated hydrocarbon, as a secondary factor.
Demand response through automated air conditioning in commercial buildings—a data-driven approach
Authors: Drasch Benedict J. , Fridgen Gilbert , Häfner Lukas 
Published: September 2020

AbstractBuilding operation faces great challenges in electricity cost control as prices on electricity markets become increasingly volatile. Simultaneously, building operators could nowadays be empowered with information and communication technology that dynamically integrates relevant information sources, predicts future electricity prices and demand, and uses smart control to enable electricity cost savings. In particular, data-driven decision support systems would allow the utilization of temporal flexibilities in electricity consumption by shifting load to times of lower electricity prices. To contribute to this development, we propose a simple, general, and forward-looking demand response (DR) approach that can be part of future data-driven decision support systems in the domain of building electricity management. For the special use case of building air conditioning systems, our DR approach decides in periodic increments whether to exercise air conditioning in regard to future electricity prices and demand. The decision is made based on an ex-ante estimation by comparing the total expected electricity costs for all possible activation periods. For the prediction of future electricity prices, we draw on existing work and refine a prediction method for our purpose. To determine future electricity demand, we analyze historical data and derive data-driven dependencies. We embed the DR approach into a four-step framework and demonstrate its validity, utility and quality within an evaluation using real-world data from two public buildings in the US. Thereby, we address a real-world business case and find significant cost savings potential when using our DR approach.
Distinction of Students and Expert Therapists Based on Therapeutic Motions on a Robotic Device Using Support Vector Machine
Authors: Yuji Koike , Makoto Suzuki , Akihisa Okino , Kazuhisa Takeda , Yasuhiro Takanami , Toyohiro Hamaguchi 
Published: September 2020

Abstract
Purpose
To clarify the feature values of exercise therapy that can differentiate students and expert therapists and use this information as a reference for exercise therapy education.

Methods
The participants were therapists with 5 or more years of clinical experience and 4th year students at occupational therapist training schools who had completed their clinical practices. The exercise therapy task included Samothrace (code name, SAMO) exercises implemented on the elbow joint based on the elbow flexion angle, angular velocity, and exercise interval recordings. For analyses and student/therapist comparisons, the peak flexion angle, peak velocity, and movement time were calculated using data on elbow angle changes acquired via SAMO. Subsequently, bootstrap data were generated to differentiate between the exercise therapy techniques adopted by therapists and students, and a support vector machine was used to generate four types of data combinations with the peak flexion angle, peak velocity, and movement time values. These data were used to estimate and compare the respective accuracies with the Friedman test.

Results
The peak flexion angles were significantly smaller in the case of students. Furthermore, the peak velocities were larger, the peak flexion angles were smaller, and the movement times were shorter compared with those of therapists. The combination of peak velocity and peak flexion angle yielded the highest diagnostic accuracies.

Conclusion
When students and therapists performed upper limb exercise therapy techniques based on the kinematics movement of a robot arm, the movement speeds and joint angles differed. The combination of peak velocity and peak flexion angle was the most effective classifier used for the differentiation of the abilities of students and therapists. The peak velocity and peak flexion angle of the therapist group can be used as a reference for students when they learn upper limb therapeutic exercise techniques.
Digital biofabrication to realize the potentials of plant roots for product design
Authors: Zhou Jiwei , Barati Bahareh , Wu Jun , Scherer Diana , Karana Elvin 
Published: September 2020

AbstractTechnological and economic opportunities, alongside the apparent ecological benefits, point to biodesign as a new industrial paradigm for the fabrication of products in the twenty-first century. The presented work studies plant roots as a biodesign material in the fabrication of self-supported 3D structures, where the biologically and digitally designed materials provide each other with structural stability. Taking a material-driven design approach, we present our systematic tinkering activities with plant roots to better understand and anticipate their responsive behaviour. These helped us to identify the key design parameters and advance the unique potential of plant roots to bind discrete porous structures. We illustrate this binding potential of plant roots with a hybrid 3D object, for which plant roots connect 600 computationally designed, optimized, and fabricated bioplastic beads into a low stool.
Acetylcholinesterase inhibitors and antioxidants mining from marine fungi: bioassays, bioactivity coupled LC–MS/MS analyses and molecular networking
Authors: Nie Yingying , Yang Wencong , Liu Yayue , Yang Jingming , Lei Xiaoling , Gerwick William H. , Zhang Yi 
Published: September 2020

AbstractMarine fungi are potentially important resources for bioactive lead compounds for discovering new drugs for diseases such as Alzheimer’s disease. In this paper, the combined bioassay model of acetylcholinesterase (AChE) inhibition, 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging, and Artemia larval lethality was used to evaluate the activity and toxicity of 35 marine fungal strains from seas around China. Their bioactive constituents were revealed by thin layer chromatography (TLC) autography, bioactivity coupled LC–MS/MS and Global Natural Products Social Molecular Networking (GNPS). The results show that the extracts of five strains exhibited higher AChE inhibition ratios than the positive control compound, ‘tacrine’, for which the ratio was 89.8% at 200 μg/ml. Six strains displayed both AChE inhibition (inhibition ratios > 20% at 200 μg/ml) and DPPH scavenging activity (scavenging ratios > 30% at 200 μg/ml) together with low Artemia larval toxicity (lethal rates < 12%). TLC autography showed that the fractioned extracts of four strains contained highly diverse and different bioactive constituents, including strains Talaromyces sp. C21-1, Aspergillus terreus C23-3, Trichoderma harzianum DLEN2008005, and Penicillium corylophilum TBG1-17. From the most potent sample F-11-1-b (derived from Aspergillus terreus C23-3), five AChE inhibitors and seven antioxidants were recognized as bioactive molecules by AChE coupled ultrafiltration followed by LC–MS/MS, and LC–MS/MS coupled with DPPH incubation. Furthermore, with the aid of GNPS, the AChE inhibitors were plausibly annotated as territrem analogues including territrems A–C/D, arisugacin A and an unknown compound 4, and the seven antioxidants were assigned as butyrolactone Ι, aspernolide E, a phenolic derivative and possibly unknown compounds 8–10 and 12.
An innovative program to provide methodological mentoring and to foster the development of robust research teams for K awardees: RAMP Mentors
Authors: Rasmussen-Torvik Laura J. , Daniels Lauren A. , Herzog Keith A. , Traw Emily J. , Fleming Michael F. , Pope Richard M. , Lloyd-Jones Donald M. , Welty Leah J. 
Published: September 2020

Abstract
Within the Biostatistics, Epidemiology, and Research Design (BERD) component of the Northwestern University Clinical and Translational Sciences Institute, we created a mentoring program to complement training provided by the associated Multidisciplinary Career Development Program (KL2). Called Research design Analysis Methods Program (RAMP) Mentors, the program provides each KL2 scholar with individualized, hands-on mentoring in biostatistics, epidemiology, informatics, and related fields, with the goal of building multidisciplinary research teams. From 2015 to 2019, RAMP Mentors paired 8 KL2 scholars with 16 individually selected mentors. Mentors had funded/protected time to meet at least monthly with their scholar to provide advice and instruction on methods for ongoing research, including incorporating novel techniques. RAMP Mentors has been evaluated through focus groups and surveys. KL2 scholars reported high satisfaction with RAMP Mentors and confidence in their ability to establish and maintain methodologic collaborations. Compared with other Northwestern University K awardees, KL2 scholars reported higher confidence in obtaining research funding, including subsequent K or R awards, and selecting appropriate, up-to-date research methods. RAMP Mentors is a promising partnership between a BERD group and KL2 program, promoting methodologic education and building multidisciplinary research teams for junior investigators pursuing clinical and translational research.