bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delayed crises following benzodiazepine withdrawal: deficient adaptive mechanisms or simple pharmacokinetics? Detoxification assisted by serum-benzodiazepine elimination tracking
Authors: Basińska-Szafrańska Anna 
Published: September 2021

Abstract
Objective
Rapid relapses after successful withdrawal occur even in apparently motivated benzodiazepine (BZD)-dependent patients. Regardless of known personality or biological (re-adaptation) issues, the aim of this open-label, single-arm, seminaturalistic study was to search for any detoxification errors contributing to failures.

Methods
The data came from 350 inpatients. Based on serum-BZD evolution criteria, the procedure was divided into four stages: substitution, accumulation, elimination and post-elimination observation. After switching the patients to a long-acting substitute (diazepam), to prevent data falsification due to unwanted overaccumulation, the doses were expeditiously reduced under laboratory feedback until accumulation stopped. With the start of effective elimination, the tapering rate slowed and was individually adjusted to the patient’s current clinical state. The tracking of both serum-BZD concentration and the corresponding intensity of withdrawal symptoms was continued throughout the entire elimination phase, also following successful drug withdrawal. Detoxification was concluded only after the patient's post-elimination stabilization.

Results
Regardless of various initial serum-BZD concentration levels and the customized dose-reduction rate, and despite the novel lab-driven actions preventing initial overaccumulation, elimination was systematically proven to be protracted and varied within the 2- to 95-day range after the final dose. Within this period, withdrawal syndrome culminated several times, with varying combinations of symptoms. The last crisis occurrence (typically 2–3 weeks after withdrawal) correlated with the final serum-BZD elimination. The factors that prolonged elimination and delayed the final crisis were patient age, duration of addiction, adjunct valproate medication and elimination stage start parameters growing with former overaccumulation.

Conclusions
The low-concentration detoxification stage is critical for patients’ confrontations with recurring withdrawal symptoms. Underestimated elimination time following drug withdrawal and premature conclusions of detoxification expose patients to unassisted withdrawal crises. Concentration tracking defines proper limits for medical assistance, preventing early relapses.
Computational Fluid Dynamics Modeling of Liver Radioembolization: A Review
Authors: Aramburu Jorge , Antón Raúl , Rodríguez-Fraile Macarena , Sangro Bruno , Bilbao José Ignacio 
Published: September 2021

AbstractYttrium-90 radioembolization (RE) is a widely used transcatheter intraarterial therapy for patients with unresectable liver cancer. In the last decade, computer simulations of hepatic artery hemodynamics during RE have been performed with the aim of better understanding and improving the therapy. In this review, we introduce the concept of computational fluid dynamics (CFD) modeling with a clinical perspective and we review the CFD models used to study RE from the fluid mechanics point of view. Finally, we show what CFD simulations have taught us about the hemodynamics during RE, the current capabilities of CFD simulations of RE, and we suggest some future perspectives.
White Blood Cells in Patients Treated with Programmed Cell Death-1 Inhibitors for Non-small Cell Lung Cancer
Authors: Sibille A. , Henket M. , Corhay J. L. , Alfieri R. , Louis R. , Duysinx B. 
Published: September 2021

Abstract
Purpose
To investigate whether eosinophils and other white blood cell subtypes could be used as response and prognostic markers to anti-Programmed cell Death-1 or anti-PD-Ligand-1 treatments in non-small cell lung cancer patients.

Methods
We retrospectively analyzed data from the NSCLC patients consecutively treated at our hospital with a PD-1/PD-L1 inhibitor in monotherapy for advanced disease. A total of 191 patients were evaluated at three time-points to investigate any relation between tumor response and WBC counts.

Results
Baseline WBC and subtypes did not differ according to the type of response seen under treatment. A higher relative eosinophil count (REC) correlated with more objective responses (p = 0.019 at t1 and p = 0.014 at t2; OR for progression = 0.54 and 0.53, respectively) independently of the smoking status, PD-L1 status, and immune-related toxicity (IRT). Higher REC was also associated with a longer duration of treatment (p = 0.0096). Baseline absolute neutrophil count was prognostic (p = 0.049). At t1 relative lymphocytes, absolute and relative neutrophils, and neutrophil-to-lymphocyte ratio were prognostic (p = 0.044, p = 0.014, p = 0.0033, and p = 0.029, respectively).

Conclusion
Our results show that in NSCLC patients anti-PD-1/PD-L1 therapy induces an early increase only in blood eosinophils, more prominent in responding patients and independent of the smoking status, PD-L1 status, and IRT. Eosinophils are also associated with a longer duration of treatment. Furthermore, our data support a prognostic role of neutrophils, lymphocytes, and their ratio for NSCLC patients with advanced disease treated with PD(L)-1 blockade.
Response time and response time variability as indicators of response quality during static automated perimetry
Authors: Ungewiss Judith , Mallot Hanspeter A. , Schiefer Ulrich 
Published: September 2021

Abstract
Purpose
Perimetry is a both demanding and strenuous examination method that is often accompanied by signs of fatigue, leading to false responses and thus incorrect results. Therefore, it is essential to monitor the response quality. The purpose of this study was to evaluate the response time (RT) and its variability (RTV) as quality indicators during static automated perimetry.

Methods
Size III Goldmann stimuli (25.7′) were shown with the OCTOPUS 900 perimeter in four visual field locations with 13 different stimulus luminance levels (0.04–160 cd/m2). An increased rate of false-positive and false-negative catch trials (25% each) served to monitor the response quality simultaneously together with response time recording. Data evaluation was divided into global and individual analysis. For global analysis, the agreement indices (AI, agreement between time periods with an increased number of false responses to catch trials and time periods with pathological response to time-based values set into relation to time periods in which only one of the two criteria was considered pathological) and for individual analysis, the Spearman correlation coefficients were calculated. Ophthalmologically normal subjects with a visual acuity ≥ 0.8, and a maximum spherical/cylindrical ametropia of ± 8.00/2.50 dpt were included.

Results
Forty-eight subjects (18 males, 30 females, age 22–78 years) were examined. The total number of false responses to catch trials was (median/maximum): 6/82. RT and RTV were compared to the occurrence of incorrect responses to catch trials. The resulting individual Spearman correlation coefficients (median/maximum) were for RT: ρRT = 0.05/0.35 and for RTV: ρRTV = 0.27/0.61. The global analysis of the RTV showed agreement indices (median/maximum) of AIRTV = 0.14/0.47.

Conclusions
According to this study, an increased portion of catch trials is suitable as a verification tool for possible response quality indicators. The RTV is a promising parameter for indicating the response quality.
Age-related declines in muscle and respiratory function are proportionate to declines in performance in Master Track Cyclists
Authors: Ocana Pablo Duro , Darabseh Mohammad Z. , Ishihara Kengo , Aburub Aseel , Zambolin Fabio , Montgomery Gallin , Mills Richard , Scorcelletti Matteo , Cameron James , Ganse Bergita , Degens Hans , Bagley Liam 
Published: September 2021

Abstract
Purpose
Respiratory and musculoskeletal function decline with age, irrespective of physical activity levels. Previous work has suggested that the age-related rate of decline in function of these two systems might be similar, but it is not known to what extent each system contributes to decreasing performance in ageing master cyclists. Therefore, the purposes of this study are (1) whether the age-related rate of decline in respiratory function, respiratory muscle strength, muscle architecture, muscle function, haemoglobin concentration, haematocrit and performance in master cyclists is uniform and (2) which parameters contribute most to the reduction in performance with age.

Methods
Master cyclists were recruited during the Track Cycling Masters World Championship 2019 in Manchester. Respiratory function and respiratory muscle strength were determined using spirometry and a mouth pressure device, respectively. Muscle architecture was determined using ultrasonography, and muscle function by countermovement jump.

Results
Forced expiratory volume in the first second, forced vital capacity, fascicle length, muscle thickness, take-off velocity, jump power, jump power per body mass, handgrip strength, haemoglobin concentration and performance correlated negatively with age (p ≤ 0.043). The age-related rate of decline did not differ significantly between parameters (p = 0.124), but it was slower for haemoglobin concentration (p = 0.041). Take-off velocity was the major determinant of performance in 200, 500 and 2000 m track cycling disciplines (R2adj = 0.675, 0.786 and 0.769, respectively; p < 0.001).

Conclusion
Age-related decline in respiratory and muscle system is accompanied by a similar rate of decline in performance. The major contribution to the age-related decline of performance is reduced muscle function, specifically take-off velocity.
Finnish Version of the Eating Assessment Tool (F-EAT-10): A Valid and Reliable Patient-reported Outcome Measure for Dysphagia Evaluation
Authors: Järvenpää Pia , Kuuskoski Jonna , Pietarinen Petra , Markkanen-Leppänen Mari , Freiberg Hanna , Ruuskanen Miia , Rekola Jami , Ilmarinen Taru , Kinnari Teemu J. , Autio Timo J. , Penttilä Elina , Muttilainen Marika S. , Laaksonen Annika , Oksanen Lotta , Geneid Ahmed , Aaltonen Leena-Maija 
Published: September 2021

AbstractOur aim was to validate a Finnish version of the Eating Assessment Tool (F-EAT-10) for clinical use and to test its reliability and validity in a multicenter nationwide study. Normative data were acquired from 180 non-dysphagic participants (median age 57.0 years, 62.2% female). Dysphagia patients (n = 117, median age 69.7 years, 53.0% female) referred to fiberoptic endoscopic evaluation of swallowing (FEES) completed F-EAT-10 before the examination and after 2 weeks. Patients underwent the 100-ml water swallow test (WST) and FEES was evaluated using the following three scales: the Yale Pharyngeal Residue Severity Rating Scale, Penetration-Aspiration Scale, and the Dysphagia Outcome Severity Scale. An operative cohort of 19 patients (median age 75.8 years, 57.9% female) underwent an endoscopic operation on Zenker’s diverticulum, tight cricopharyngeal muscle diagnosed in videofluorography, or both. Patients completed the F-EAT-10 preoperatively and 3 months postoperatively. The cut-off score for controls was < 3 (sensitivity 94.0%, specificity 96.1%) suggesting that ≥ 3 is abnormal. Re-questionnaires for test–retest reliability analysis were available from 92 FEES patients and 123 controls. The intraclass correlation coefficient was excellent for the total F-EAT-10 score (0.93, 95% confidence interval 0.91–0.95). Pearson correlation coefficients were strong (p < 0.001) for each of the questions and the total score. Internal consistency as assessed by Cronbach’s alpha was excellent (0.95). Some correlations between findings in FEES and 100-ml WST with F-EAT-10 were observed. The change in subjective symptoms of operative patients paralleled the change in F-EAT-10. F-EAT-10 is a reliable, valid, and symptom-specific patient-reported outcome measure for assessing dysphagia among Finnish speakers.
Increasing the safety against scuffing of additive manufactured gear wheels by internal cooling channels
Authors: Dennig Hans-Jörg , Zumofen Livia , Stierli Daniel , Kirchheim Andreas , Winterberg Simon 
Published: September 2021

AbstractThe layer-by-layer principle of the additive manufacturing (AM) technology of Laser-Powder-Bed-Fusion (LPBF) creates new opportunities in the design and manufacturing of efficient gear components. For example, integrating a cooling system can increase the safety against scuffing or reduce the amount of required lubrication and thus the splashing losses. Quenched and tempered steels or case-hardened steels are commonly used in the fabrication of gear components. However, the availability of these alloys for LPBF processing is still limited. The development of suitable LPBF metal gears (with a Gear Research Centre (FZG) type A geometry) out of quenched and tempered 30CrNiMo8 steel with internal cooling channels shows the possibility of significantly increasing the safety factor against scuffing. This work includes the development of a suitable cooling strategy, material development, the setup of a suitable test infrastructure and the analysis of the LPBF gears tested for scuffing.
Weighted stochastic block model
Authors: Ng Tin Lok James , Murphy Thomas Brendan 
Published: September 2021

AbstractWe propose a weighted stochastic block model (WSBM) which extends the stochastic block model to the important case in which edges are weighted. We address the parameter estimation of the WSBM by use of maximum likelihood and variational approaches, and establish the consistency of these estimators. The problem of choosing the number of classes in a WSBM is addressed. The proposed model is applied to simulated data and an illustrative data set.
Entanglement and U(D)-spin squeezing in symmetric multi-quDit systems and applications to quantum phase transitions in Lipkin–Meshkov–Glick D-level atom models
Authors: Calixto Manuel , Mayorgas Alberto , Guerrero Julio 
Published: September 2021

AbstractCollective spin operators for symmetric multi-quDit (namely identical D-level atom) systems generate a U(D) symmetry. We explore generalizations to arbitrary D of SU(2)-spin coherent states and their adaptation to parity (multi-component Schrödinger cats), together with multi-mode extensions of NOON states. We write level, one- and two-quDit reduced density matrices of symmetric N-quDit states, expressed in the last two cases in terms of collective U(D)-spin operator expectation values. Then, we evaluate level and particle entanglement for symmetric multi-quDit states with linear and von Neumann entropies of the corresponding reduced density matrices. In particular, we analyze the numerical and variational ground state of Lipkin–Meshkov–Glick models of 3-level identical atoms. We also propose an extension of the concept of SU(2)-spin squeezing to SU(D) and relate it to pairwise D-level atom entanglement. Squeezing parameters and entanglement entropies are good markers that characterize the different quantum phases, and their corresponding critical points, that take place in these interacting D-level atom models.
Necroptosis increases with age in the brain and contributes to age-related neuroinflammation
Authors: Thadathil Nidheesh , Nicklas Evan H. , Mohammed Sabira , Lewis Tommy L. , Richardson Arlan , Deepa Sathyaseelan S. 
Published: September 2021

AbstractChronic inflammation of the central nervous system (CNS), termed neuroinflammation, is a hallmark of aging and a proposed mediator of cognitive decline associated with aging. Neuroinflammation is characterized by the persistent activation of microglia, the innate immune cells of the CNS, with damage-associated molecular patterns (DAMPs) being one of the well-known activators of microglia. Because necroptosis is a cell death pathway that induces inflammation through the release of DAMPs, we hypothesized that an age-associated increase in necroptosis contributes to increased neuroinflammation with age. The marker of necroptosis, phosphorylated form of MLKL (P-MLKL), and kinases in the necroptosis pathway (RIPK1, RIPK3, and MLKL) showed a region-specific increase in the brain with age, specifically in the cortex layer V and the CA3 region of the hippocampus of mice. Similarly, MLKL-oligomers, which cause membrane binding and permeabilization, were significantly increased in the cortex and hippocampus of old mice relative to young mice. Nearly 70 to 80% of P-MLKL immunoreactivity was localized to neurons and less than 10% was localized to microglia, whereas no P-MLKL was detected in astrocytes. P-MLKL expression in neurons was detected in the soma, not in the processes. Blocking necroptosis using Mlkl−/− mice reduced markers of neuroinflammation (Iba-1 and GFAP) in the brains of old mice, and short-term treatment with the necroptosis inhibitor, necrostatin-1s, reduced expression of proinflammatory cytokines, IL-6 and IL-1β, in the hippocampus of old mice. Thus, our data demonstrate for the first time that brain necroptosis increases with age and contributes to age-related neuroinflammation in mice.
Paternal environmental exposure-induced spermatozoal small noncoding RNA alteration meditates the intergenerational epigenetic inheritance of multiple diseases
Authors: Yin Xin , Anwar Azhar , Wang Yanbo , Hu Huanhuan , Liang Gaoli , Zhang Chenyu 
Published: September 2021

AbstractStudies of human and mammalian have revealed that environmental exposure can affect paternal health conditions as well as those of the offspring. However, studies that explore the mechanisms that meditate this transmission are rare. Recently, small noncoding RNAs (sncRNAs) in sperm have seemed crucial to this transmission due to their alteration in sperm in response to environmental exposure, and the methodology of microinjection of isolated total RNA or sncRNAs or synthetically identified sncRNAs gradually lifted the veil of sncRNA regulation during intergenerational inheritance along the male line. Hence, by reviewing relevant literature, this study intends to answer the following research concepts: (1) paternal environmental factors that can be passed on to offspring and are attributed to spermatozoal sncRNAs, (2) potential role of paternal spermatozoal sncRNAs during the intergenerational inheritance process, and (3) the potential mechanism by which spermatozoal sncRNAs meditate intergenerational inheritance. In summary, increased attention highlights the hidden wonder of spermatozoal sncRNAs during intergenerational inheritance. Therefore, in the future, more studies should focus on the origin of RNA alteration, the target of RNA regulation, and how sncRNA regulation during embryonic development can be sustained even in adult offspring.
COVID-19 and Organized Crime: Strategies employed by criminal groups to increase their profits and power in the first months of the pandemic
Authors: Aziani Alberto , Bertoni Gianluca A. , Jofre Maria , Riccardi Michele 
Published: September 2021

AbstractThe COVID-19 pandemic has created new opportunities for organized criminal groups and confronted them with new challenges. Analysis of how these groups have reacted to the pandemic yields better understanding of how they work and enables the devising of more effective counter-strategies. To this end, we identified illustrative cases regarding the provision of illegal governance and infiltration of the legal economy by conducting a systematic content analysis of international media articles and institutional reports published during the first eight months after the outbreak of the pandemic (January to August 2020). These cases were further analyzed in order to cluster the behavior of criminal groups in response to the COVID-19 emergency, and the means by which they tried to exploit the pandemic to strengthen their political and economic power. We found that different governance-type criminal groups proposed themselves as institutions able to mitigate the burdens imposed by the pandemic by providing support to people in need and enforcing social-distancing measures. Further, identified cases did not provide evidence of groups devoted to the provision of illicit services and goods assuming any governance role. In this respect, the available evidence supports previous knowledge about organized crime. Cases of misappropriation of public funds and organized crime infiltration of the legal economy seem less common, at least in the first phase of the pandemic. The wholesale distribution of pharmaceuticals and medicines has been the sector targeted the most.
Visual analytics for nonlinear programming in robot motion planning
Authors: Hägele David , Abdelaal Moataz , Oguz Ozgur S. , Toussaint Marc , Weiskopf Daniel 
Published: September 2021

Abstract
Nonlinear programming is a complex methodology where a problem is mathematically expressed in terms of optimality while imposing constraints on feasibility. Such problems are formulated by humans and solved by optimization algorithms. We support domain experts in their challenging tasks of understanding and troubleshooting optimization runs of intricate and high-dimensional nonlinear programs through a visual analytics system. The system was designed for our collaborators’ robot motion planning problems, but is domain agnostic in most parts of the visualizations. It allows for an exploration of the iterative solving process of a nonlinear program through several linked views of the computational process. We give insights into this design study, demonstrate our system for selected real-world cases, and discuss the extension of visualization and visual analytics methods for nonlinear programming.

Graphic abstract
Stabilization of the vertical take-off of a rigid flying wing for an airborne wind energy system
Authors: Fuest H. , Duda D. F. , Islam T. , Ostermann T. , Moormann D. 
Published: September 2021

AbstractAirborne wind energy is an emerging technology that harvests wind energy with flight systems connected via a tether to the ground. In the project “EnerGlider”, a flying wing is meant to fly fully automated by its own control units. This contribution discusses the challenges to control and trim this flying wing during vertical take-off and landing under the influence of a horizontal wind velocity. High wind velocities can lead to unstable and untrimmed states concerning the longitudinal motion of the flying wing. The paper analyzes the influence of design modifications of thrust vector and elevon area to enhance the flight envelope of the trimmed states to higher wind velocities. Besides, the tether force as additional control unit is considered for strong wind forces. It is demonstrated that a tether force acting behind the center of gravity can significantly enhance the robustness of the flight system concerning wind velocity. Moreover, the unstable flight states emerging during vertical take-off and landing can be stabilized with a flight control.