bluuebunny/crossref_metadata_2025 huggingface dataset:
Physikalische Interventionen als Alternative/Ergänzung zum chirurgischen Wunddebridement
Authors: Werra Ursula Elisabeth Maria , Zinser Max , Dorweiler Bernhard
Published: December 2021

Hintergrund

Die Versorgung von Patienten mit chronischen Wunden verursacht in Deutschland jährliche Kosten in Höhe von 8 Mrd. €.

Häufig ist ein chirurgisches Debridement notwendig. Wenn jedoch kritische Strukturen lokal angrenzen oder der Patient nur eingeschränkt narkosefähig ist, können die Einsatzmöglichkeiten limitiert sein.

Zusätzlich ist aus wirtschaftlichen Gründen eine mögliche Delegierbarkeit immer von Interesse.

Fragestellung

Wir präsentieren alternative sowie ergänzende Methoden zum chirurgischen Debridement aus dem Portfolio der physikalischen Interventionen.

Material und Methoden

Ultraschallassistiertes Wunddebridement (UAW), Kaltplasma sowie Photobiomodulation basieren auf interessanten Grundprinzipien mit vielversprechendem Entwicklungspotenzial. Der Wirkmechanismus, die Evidenzlage sowie wirtschaftliche Aspekte werden vorgestellt.

Ergebnisse

Es zeigt sich insgesamt aufgrund der Inhomogenität der Daten eine nur schwache Evidenzlage. Auch einige Aspekte der Behandlungsmodalitäten sind noch nicht abschließend geklärt.

Das UAW stellt eine echte Alternative dar. Es erfährt eine hohe Patientenakzeptanz und ist ambulant durchführbar.

Die Wirksamkeit von Kaltplasma oder Photobiomodulation ist noch nicht abschließend beurteilbar. Es zeigen sich jedoch positive klinische Ergebnisse.

Diskussion

Das chirurgische Debridement ist auch aktuell (noch) nicht vollständig ersetzbar. Alternative Methoden wie das UAW können jedoch einen zusätzlichen Benefit bieten. Wunden können so teilweise frühzeitig (mit entsprechender Kostenersparnis) ambulant behandelt werden. Eine weitere wichtige Stärke stellt zudem die Wirksamkeit bezüglich multiresistenter Erreger dar.

Es besteht die Notwendigkeit zur Initiierung weiterer klinischer Studien, da die aktuelle Datenlage noch viele offene Fragen aufweist.
Untersuchung und Klassifikation der Fahreraufmerksamkeit bei längerer partiell automatisierter Fahrt
Authors: Hugenroth Alexander , Warnecke Alexander , Bertram Torsten
Published: December 2021

Um die Unfallzahlen weiter zu senken, schreibt die Europäische Union ab 2030 eine höhere Fahrerüberwachung für neue Fahrzeuge vor. Bislang liegt der Fokus in einem manuell gefahrenen Fahrzeug auf einer Müdigkeitserkennung als Komfortsystem. Jedoch ändern sich die Anforderungen an den Fahrer und dessen Aufgaben bei steigender Automatisierung der Fahraufgabe, sodass auch die Fahrerbeobachtung/-überwachung weiter entwickelt werden sollte. Die vorliegende Arbeit beschäftigt sich mit der Auslegung von Aufmerksamkeitsaufgaben in Simulator-Fahrversuchen und einem ersten Versuch die aufgenommenen Daten von wenigen Probanden automatisch auszuwerten, um die Machbarkeit zu zeigen. Durch die partielle Automatisierung (nach SAE Level 2) der Fahraufgabe bleiben dem Fahrer bei der hier vorgestellten längeren Aufmerksamkeitsaufgabe nur noch schwache und seltene Reize, sodass von einer Vigilanzaufgabe gesprochen werden kann. Zur Messung des Fahrerzustands wird in dieser Machbarkeitsstudie eine Kombination aus verschieden Körperfunktionen durch unterschiedliche Sensoren erfasst, mit einem künstlichen neuronalen Netzwerk fusioniert und verarbeitet. Es werden verschiedene Kombinationen von Sensoren getestet, um herauszufinden, welche Signale für eine Klassifikation des Fahrerzustands ausreichend oder notwendig sind. Dabei wird darauf geachtet, ob diese Signale in Zukunft durch neue Sensortechnologien auch kontaktlos erfasst werden könnten, um eine Entwicklung dieser zu motivieren. Am Ende wird eine Klassifizierung vorgenommen, die zwischen den hier so genannten Zuständen Vigilant (aufmerksam) und Hypovigilant (nicht mehr aufmerksam) unterscheiden kann, sodass eine anschließende Regelung ein solches Signal verwenden kann, um den Fahrer in einen besseren Zustand zu bringen. Zudem kann der Fahrer gewarnt werden, wenn die Aufmerksamkeit nicht zu den Aufgaben passt, die er in der Automatisierungsstufe zu erledigen hat beziehungsweise für die er verantwortlich ist. Dazu könnten Aufgaben zwischen dem Fahrzeug und dem Fahrer dynamisch verteilt werden, also beispielsweise die Führung in Längs- oder Querrichtung wieder als Fahraufgabe dem Fahrer übergeben werden, um ihn aufmerksam zu halten. Durch eine kontaktlose Erfassung der Aufmerksamkeit gibt es zudem einen Komfortgewinn, da zum Beispiel die Hände nicht mehr das Lenkrad festhalten müssen, um dem Fahrzeug seine Aufmerksamkeit zu bestätigen, wie es heute in einigen Fahrzeugen üblich ist.
Recent Lateral Expansion of Sphagnum Bogs Over Central Fen Areas of Boreal Aapa Mire Complexes
Authors: Granlund Lars , Vesakoski Ville , Sallinen Antti , Kolari Tiina H. M. , Wolff Franziska , Tahvanainen Teemu
Published: December 2021

We investigated recent changes in spatial patterning of fen and bog zones in five boreal aapa mire complexes (mixed peatlands with patterned fen and bog parts) in a multiproxy study. Comparison of old (1940–1970s) and new aerial images revealed decrease of flarks (wet hollows) in patterned fens by 33–63% in middle boreal and 16–42% in northern boreal sites, as lawns of bog Sphagnum mosses expanded over fens. Peat core transects across transformed areas were used to verify the remote sensing inference with stratigraphic analyses of macrofossils, hyperspectral imaging, and age-depth profiles derived from 14C AMS dating and pine pollen density. The transect data revealed that the changes observed by remote sensing during past decades originated already from the end of the Little Ice Age (LIA) between 1700–1850 CE in bog zones and later in the flarks of fen zones. The average lateral expansion rate of bogs over fen zones was 0.77 m y−1 (range 0.19–1.66) as estimated by remote sensing, and 0.71 m y−1 (range 0.13–1.76) based on peat transects. The contemporary plant communities conformed to the macrofossil communities, and distinct vegetation zones were recognized as representing recently changed areas. The fen-bog transition increased the apparent carbon accumulation, but it can potentially threaten fen species and habitats. These observations indicate that rapid lateral bog expansion over aapa mires may be in progress, but more research is needed to reveal if ongoing fen-bog transitions are a commonplace phenomenon in northern mires.
Tree Diversity, Initial Litter Quality, and Site Conditions Drive Early-Stage Fine-Root Decomposition in European Forests
Authors: Wambsganss Janna , Freschet Grégoire T. , Beyer Friderike , Bauhus Jürgen , Scherer-Lorenzen Michael
Published: December 2021

Decomposition of dead fine roots contributes significantly to nutrient cycling and soil organic matter stabilization. Most knowledge of tree fine-root decomposition stems from studies in monospecific stands or single-species litter, although most forests are mixed. Therefore, we assessed how tree species mixing affects fine-root litter mass loss and which role initial litter quality and environmental factors play. For this purpose, we determined fine-root decomposition of 13 common tree species in four European forest types ranging from boreal to Mediterranean climates. Litter incubations in 315 tree neighborhoods allowed for separating the effects of litter species from environmental influences and litter mixing (direct) from tree diversity (indirect). On average, mass loss of mixed-species litter was higher than those of single-species litter in monospecific neighborhoods. This was mainly attributable to indirect diversity effects, that is, alterations in microenvironmental conditions as a result of tree species mixing, rather than direct diversity effects, that is, litter mixing itself. Tree species mixing effects were relatively weak, and initial litter quality and environmental conditions were more important predictors of fine-root litter mass loss than tree diversity. We showed that tree species mixing can alter fine-root litter mass loss across large environmental gradients, but these effects are context-dependent and of moderate importance compared to environmental influences. Interactions between species identity and site conditions need to be considered to explain diversity effects on fine-root decomposition.
After the smoke has cleared: Extended low fruit productivity following forest fires decreased gregariousness and social tolerance among wild female Bornean orangutans (Pongo pygmaeus wurmbii)
Authors: Ashbury Alison M. , Meric de Bellefon Jade , Kunz Julia A. , Abdullah Misdi , Marzec Anna M. , Fryns Caroline , Utami Atmoko Sri Suci , van Schaik Carel P. , van Noordwijk Maria A.
Published: December 2021

As climate change continues to fundamentally alter resource landscapes, the ability to flexibly respond to spatio-temporal changes in the distribution of preferred food sources is increasingly important for the overall health and fitness of animals living in seasonal, variable, and/or changing environments. Here, we investigate the effects of an uncharacteristically long period of fruit scarcity, following widespread thick haze caused by peat and forest fires in 2015, on the behaviour and sociality of female Bornean orangutans (Pongo pygmaeus wurmbii). We collected data from 2010 to 2018 at Tuanan, Central Kalimantan, Indonesia, and compared the activity, diet, and association patterns of adult females during low-fruit periods before the fires, i.e., regular, seasonal periods of low fruit availability (“pre-fire”), and after the fires, i.e., during the extended period of low fruit availability (“post-fire”). First, we found that, post-fire, female orangutans adopted a more extreme energy-saving activity pattern and diet — resting more, travelling less, and diet-switching to less-preferred foods — compared to pre-fire. Second, we found that the probabilities of association between females and their weaned immature offspring, and between related and unrelated adult females were lower, and the probability of agonism between unrelated females was higher, post-fire than pre-fire. This change in energetic strategy, and the general reduction in gregariousness and social tolerance, demonstrates how forest fires can have lasting consequences for orangutans. Fission–fusion species such as orangutans can mitigate the effects of changes in resource landscapes by altering their (sub)grouping patterns; however, this may have long-term indirect consequences on their fitness.
Ratcheting and recovery of adhesively bonded joints under tensile cyclic loading
Authors: Chen Yi , Smith Lloyd V.
Published: December 2021

Polymers in general, and adhesives in particular, can exhibit nonlinear viscoelastic–viscoplastic response. Prior work has shown that this complex behavior can be described using analytical models, which provided good agreement with measured creep and recovery response. Under cyclic loading, however, some adhesives exhibit a temporal response different from what would be expected from their creep behavior. Ratcheting describes the accumulation of deformation from cyclic loading. The failure surfaces of adhesives subjected to creep and cyclic loads provide evidence of failure modes that depend on the loading history, suggesting a cause for the change in temporal response. The following considers two approaches to describe the ratcheting behavior of adhesives. Given the reduced time dependence, the first approach involved a nonlinear viscoelastic–plastic model. The second approach used a nonlinear viscoelastic–viscoplastic model, calibrated from the cyclic response, rather than the creep response. While both models showed good agreement with experiment for long exposure to cyclic loading, only the viscoelastic–viscoplastic model agreed with experiment for both short and long loading histories.
Untargeted metabolomics of COVID-19 patient serum reveals potential prognostic markers of both severity and outcome
Authors: Roberts Ivayla , Wright Muelas Marina , Taylor Joseph M. , Davison Andrew S. , Xu Yun , Grixti Justine M. , Gotts Nigel , Sorokin Anatolii , Goodacre Royston , Kell Douglas B.
Published: December 2021

Introduction

The diagnosis of COVID-19 is normally based on the qualitative detection of viral nucleic acid sequences. Properties of the host response are not measured but are key in determining outcome. Although metabolic profiles are well suited to capture host state, most metabolomics studies are either underpowered, measure only a restricted subset of metabolites, compare infected individuals against uninfected control cohorts that are not suitably matched, or do not provide a compact predictive model.

Objectives

Here we provide a well-powered, untargeted metabolomics assessment of 120 COVID-19 patient samples acquired at hospital admission. The study aims to predict the patient’s infection severity (i.e., mild or severe) and potential outcome (i.e., discharged or deceased).

Methods

High resolution untargeted UHPLC-MS/MS analysis was performed on patient serum using both positive and negative ionization modes. A subset of 20 intermediary metabolites predictive of severity or outcome were selected based on univariate statistical significance and a multiple predictor Bayesian logistic regression model was created.

Results

The predictors were selected for their relevant biological function and include deoxycytidine and ureidopropionate (indirectly reflecting viral load), kynurenine (reflecting host inflammatory response), and multiple short chain acylcarnitines (energy metabolism) among others. Currently, this approach predicts outcome and severity with a Monte Carlo cross validated area under the ROC curve of 0.792 (SD 0.09) and 0.793 (SD 0.08), respectively. A blind validation study on an additional 90 patients predicted outcome and severity at ROC AUC of 0.83 (CI 0.74–0.91) and 0.76 (CI 0.67–0.86).

Conclusion

Prognostic tests based on the markers discussed in this paper could allow improvement in the planning of COVID-19 patient treatment.
Weight smoothing for nonprobability surveys
Authors: Ferri-García Ramón , Beaumont Jean-François , Bosa Keven , Charlebois Joanne , Chu Kenneth
Published: December 2021

Adjustment techniques to mitigate selection bias in nonprobability samples often involve modelling the propensity to participate in the nonprobability sample along with inverse propensity weighting. It is well known that procedures for estimating weights are effective if the covariates selected in the propensity model are related to both the variable of interest and the participation indicator. In most surveys, there are many variables of interest, making weight adjustments difficult to determine as a suitable weight for one variable may be unsuitable for other variables. The standard compromise is to include a large number of covariates in the propensity model but this may increase the variability of the estimates, especially when some covariates are weakly related to the variables of interest. Weight smoothing, developed for probability surveys, could be helpful in these situations. It aims to remove the variability caused by overfit propensity models by replacing the inverse propensity weights with predicted weights obtained using a smoothing model. In this article, we study weight smoothing in the nonprobability survey context, both theoretically and empirically, to understand its effectiveness at improving the efficiency of estimates.
Judicial diplomacy of the German Federal Constitutional Court: bilateral court meetings as a novel data source to assess transnational communication of constitutional courts
Authors: Meyer Philipp
Published: December 2021

Judicial diplomacy describes the courts’ efforts to promote liberal democracy and protect their institutional authority. Bilateral court meetings are essential for judicial diplomacy, encompassing jurisprudential (e.g., discussion of case law) and aims of strategic (e.g., maximising influence). This study presents a novel approach to assess such meetings. It analyses the German Federal Constitutional Court meeting reports between 1998–2019, using content and semantic network analysis. The content analysis shows that court meetings focus on jurisprudential aspects; however, strategic considerations also play a role in discussions with interlocutors from emerging democracies. These findings are substantiated by the semantic network analysis, which discloses that recent case law, Europeanisation, and globalisation are the main issues discussed. Hence, this study presents an analysis of a novel data source. Further, it contributes to judicial politics research as transnational court meetings could be a missing link to understand legal citation networks.
Caffeic acid phenethyl ester (CAPE) confers wild type p53 function in p53Y220C mutant: bioinformatics and experimental evidence
Authors: Radhakrishnan Navaneethan , Dhanjal Jaspreet Kaur , Sari Anissa Nofita , Ishida Yoshiyuki , Terao Keiji , Kaul Sunil C. , Sundar Durai , Wadhwa Renu
Published: December 2021

Mutations in the tumor suppressor protein p53 is a prevalent feature in majority of cancers resulting in inactivation of its activities related to control of cell cycle progression and proliferation. p53Y220C is one of the common hotspot mutations that causes decrease in its thermodynamic stability. Some small molecules have been shown to bind to the mutated site and restore its wild type thermodynamics and tumor suppressor function. In this study, we have explored the potential of caffeic acid phenethyl ester (CAPE—a bioactive compound from propolis) to interact with p53Y220C and restore its wild type p53 (p53wt) transcription activation and tumor suppressor activities. We recruited computational methods, viz. molecular docking, molecular dynamics simulations and free energy calculations to study the interaction of CAPE at the mutation crevice and found that it has potential to restore p53wt function of the p53Y220C mutant similar to a previously described restoration molecule PK7242. We provide cell-based experimental evidence to these predictions and suggest CAPE as a potential natural drug for treatment of p53Y220C mutant harboring cancers.
Methods for separating orchards from forest using airborne LiDAR
Authors: Hycza Tomasz , Kupidura Przemysław
Published: December 2021

•Key message

The aim of the study was to distinguish orchards from other lands with forest vegetation based on the data from airborne laser scanning. The methods based on granulometry provided better results than the pattern analysis. The analysis based on the Forest Data Bank/Cadastre polygons provided better results than the analysis based on the segmentation polygons. Classification of orchards and other areas with forest vegetation is important in the context of reporting forest area to international organizations, forest management, and mitigating effects of climate change.

•Context

Agricultural lands with forest vegetation, e.g., orchards, do not constitute forests according to the forest definition formulated by the national and international definitions, but contrary to the one formulated in the Kyoto Protocol. It is a reason for the inconsistency in the forest area reported by individual countries.

•Aims

The aim of the study was to distinguish orchards from other lands with forest vegetation based on the data from airborne laser scanning.

•Methods

The study analyzed the usefulness of various laser scanning products and the various features of pattern and granulometric analysis in the Milicz forest district in Poland.

•Results

The methods based on granulometry provided better results than the pattern analysis. The analysis based on the Forest Data Bank/Cadastre polygons provided better results than the analysis based on the segmentation polygons.

•Conclusion

Granulometric analysis has proved to be a useful tool in the classification of orchards and other areas with forest vegetation. It is important in the context of reporting forest area to international organizations, forest management, and mitigating effects of climate change.
Machine remaining life prediction based on multi-layer self-attention and temporal convolution network
Authors: Shang Zhiwu , Zhang Baoren , Li Wanxiang , Qian Shiqi , Zhang Jie
Published: December 2021

Convolution neural network (CNN) has been widely used in the field of remaining useful life (RUL) prediction. However, the CNN-based RUL prediction methods have some limitations. The receptive field of CNN is limited and easy to happen gradient vanishing problem when the network is too deep. The contribution differences of different channels and different time steps to RUL prediction are not considered, and only use deep learning features or handcrafted statistical features for prediction. These limitations can lead to inaccurate prediction results. To solve these problems, this paper proposes an RUL prediction method based on multi-layer self-attention (MLSA) and temporal convolution network (TCN). The TCN is used to extract deep learning features. Dilated convolution and residual connection are adopted in TCN structure. Dilated convolution is an efficient way to widen receptive field, and the residual structure can avoid the gradient vanishing problem. Besides, we propose a feature fusion method to fuse deep learning features and statistical features. And the MLSA is designed to adaptively assign feature weights. Finally, the turbofan engine dataset is used to verify the proposed method. Experimental results indicate the effectiveness of the proposed method.
Variable universe adaptive fuzzy sliding mode projective synchronization of hyperjerk system based on disturbance observer
Authors: Zhang Baojie , Feng Yuming , Yu Hongyan , Zhang Xianxiu
Published: December 2021

In this paper, a sliding mode projective synchronization strategy based on disturbance observer and fuzzy system is presented to implement projective synchronization of hyperjerk system with low time-varying disturbance and white noise. Theoretical analysis and numerical calculation show that the disturbance observer can approach the low time-varying disturbance very well. The application of disturbance observer reduces the chattering of the controller. Variable universe adaptive fuzzy control (VUAFC) method is utilized to further reduce the chattering phenomenon. The simulation results demonstrate the effectiveness of the proposed controller.
Energy cascades in rapidly rotating and stratified turbulence within elongated domains
Authors: van Kan Adrian , Alexakis Alexandros
Published: December 2021

We study forced, rapidly rotating and stably stratified turbulence in an elongated domain using an asymptotic expansion at simultaneously low Rossby number

$\mathit {Ro}\ll 1$

and large domain height compared with the energy injection scale,

$h=H/\ell _{in}\gg 1$

. The resulting equations depend on the parameter

$\lambda =(h \mathit {Ro} )^{-1}$

and the Froude number

$\mathit {Fr}$

. An extensive set of direct numerical simulations (DNS) is performed to explore the parameter space

$(\lambda,\mathit {Fr})$

. We show that a forward energy cascade occurs in one region of this space, and a split energy cascade outside it. At weak stratification (large

$\mathit {Fr}$

), an inverse cascade is observed for sufficiently large

$\lambda$

. At strong stratification (small

$\mathit {Fr}$

) the flow becomes approximately hydrostatic and an inverse cascade is always observed. For both weak and strong stratification, we present theoretical arguments supporting the observed energy cascade phenomenology. Our results shed light on an asymptotic region in the phase diagram of rotating and stratified turbulence, which is difficult to attain by brute-force DNS.
Computed tomography analysis of the anterior ethmoid genu of the frontal recess in non-diseased sinuses
Authors: Raman K , Govindaraju R , James K , Abu Bakar M Z , Patil N , Shah M N
Published: December 2021

Objective

Knowledge of anatomical variations of the frontal recess and frontal sinus and recognition of endoscopic landmarks are vital for safe and effective endoscopic sinus surgery. This study revisited an anatomical landmark in the frontal recess that could serve as a guide to the frontal sinus.

Method

Prevalence of the anterior ethmoid genu, its morphology and its relationship with the frontal sinus drainage pathway was assessed. Computed tomography scans with multiplanar reconstruction were used to study non-diseased sinonasal complexes.

Results

The anterior ethmoidal genu was present in all 102 anatomical sides studied, independent of age, gender and race. Its position was within the frontal sinus drainage pathway, and the drainage pathway was medial to it in 98 of 102 cases. The anterior ethmoidal genu sometimes extended laterally and formed a recess bounded by the lamina papyracea laterally, by the uncinate process anteriorly and by the bulla ethmoidalis posteriorly. Distance of the anterior ethmoidal genu to frontal ostia can be determined by the height of the posterior wall of the agger nasi cell rather than its volume or other dimensions.

Conclusion

This study confirmed that the anterior ethmoidal genu is a constant anatomical structure positioned within frontal sinus drainage pathway. The description of anterior ethmoidal genu found in this study explained the anatomical connection between the agger nasi cell, uncinate process and bulla ethmoidalis and its structural organisation.
Skull base pathology – a diagnostic conundrum
Authors: Devakumar H , Cereceda-Monteoliva N , Weir J , Ferguson M
Published: December 2021

Background

Myoepithelioma is a rare benign neoplasm, most commonly derived from salivary glands, but there are limited cases of extra salivary gland involvement too. There is little knowledge on typical investigative findings and, instead, diagnosis relies on immunohistochemistry analysis. To our knowledge, this paper reports the 13th case of sinonasal myoepithelioma in the English literature.

Case report

This paper presents a 25-year-old man who complained of chronic nasal obstruction. A sinonasal mass was noted on examination that appeared benign on imaging. Biopsy revealed a grade 2 chondrosarcoma that was endoscopically resected; however, excisional margins were positive. On histopathological review at the multidisciplinary team meeting, the lesion was more in keeping with chondromyxoid fibroma, but immunohistochemistry analysis confirmed a myoepithelioma lesion. In light of this revised diagnosis, quorate opinion was for follow up with active monitoring.

Conclusion

Sinonasal tumours require a thorough history, examination and investigation before a treatment plan can be formulated. If there is diagnostic uncertainty, it is important to keep a wide differential list and seek a second specialist opinion where possible.
Toward a broader concept of societal value: family spillovers in Alzheimer's disease
Authors: Park Jenny Yeonhee , Marcum Zachary A. , Garrison Louis P.
Published: December 2021

Recognizing that the “healthcare sector perspective” can be too limited in some situations, the National Institute of Health and Care Excellence (NICE), Institute for Clinical and Economic Review (ICER), and the U.S. Second Panel on Cost-Effectiveness in Health and Medicine all recommend a “societal” perspective in “reference case” cost-effectiveness analyses (CEAs). Although costs of informal caregiving are sometimes included in the CEAs of Alzheimer's Disease (AD) drugs, the benefits and disutility to family members, referred to as “family spillovers” by the U.S. Second Panel, are usually omitted. We estimate that the aggregate cost of family spillovers could be substantial in the USA—on the order of USD 57 billion or over 10 percent of the total economic burden of AD in 2020. Incorporation of family spillovers in AD value frameworks and HTAs is important for comprehensively defining, rewarding, and providing high-value care in AD.
Application of a health technology assessment framework to digital health technologies that manage chronic disease: a systematic review
Authors: von Huben Amy , Howell Martin , Carrello Joseph , Norris Sarah , Wortley Sally , Ritchie Angus , Howard Kirsten
Published: December 2021

Background

As health services increasingly make investment decisions in digital health technologies (DHTs), a DHT-specific and comprehensive health technology assessment (HTA) process is crucial in assessing value-for-money. Research in DHTs is ever-increasing, but whether it covers the content required for HTA is unknown.

Objectives

To summarize current trends in primary research on DHTs that manage chronic disease at home, particularly the coverage of content recommended for DHT-specific and comprehensive HTA.

Methods

Medline, Embase, Econlit, CINAHL, and The Cochrane Library (1 January 2015 to 20 March 2020) were searched for primary research studies using keywords related to DHT and HTA domains. Studies were assessed for coverage of the most frequently recommended content to be considered in a nine domain DHT-specific HTA previously developed.

Results

A total of 178 DHT interventions were identified, predominantly randomized controlled trials targeting cardiovascular disease/diabetes in high- to middle-income countries. A coverage assessment of the cardiovascular and diabetes DHT studies (112) revealed less than half covered DHT-specific content in all but the health problem domain. Content common to all technologies but essential for DHTs was covered by more than half the studies in all domains except for the effectiveness and ethical analysis domains.

Conclusions

Although DHT research is increasing, it is not covering all the content recommended for a DHT-specific and comprehensive HTA. The inability to conduct such an HTA may lead to health services making suboptimal investment decisions. Measures to increase the quality of trial design and reporting are required in DHT primary research.
Childhood adversity and co-occurring post-traumatic stress and externalizing symptoms among a predominantly low-income, African American sample of early adolescents
Authors: Thompson Erin L. , O’Connor Kelly E. , Farrell Albert D.
Published: December 2021

Although there is strong evidence supporting the association between childhood adversity and symptomatology during adolescence, the extent to which adolescents present with distinct patterns of co-occurring post-traumatic stress (PTS) and externalizing symptoms remains unclear. Additionally, prior research suggests that experiencing nonviolent, negative life events may be more salient risk factors for developing some forms of psychopathology than exposure to violence. The current study used latent profile analysis to identify subgroups of early adolescents with distinct patterns of PTS, physical aggression, delinquency, and substance use, and examined subgroup differences in exposure to three forms of violent and nonviolent childhood adversity. Participants were a predominantly low-income, African American sample of 2,722 urban middle school students (M age = 12.9, 51% female). We identified four symptom profiles: low symptoms (83%), some externalizing (8%), high PTS (6%), and co-occurring PTS and externalizing symptoms (3%). A higher frequency of witnessing violence was associated with increased odds of membership in subgroups with externalizing symptoms, whereas a higher frequency of nonviolent, negative life events was associated with increased odds of membership in subgroups with PTS symptoms. Interventions aimed to address childhood adversity may be most effective when modules addressing both PTS and externalizing symptoms are incorporated.
What is the expected human childhood? Insights from evolutionary anthropology
Authors: Frankenhuis Willem E. , Amir Dorsa
Published: December 2021

In psychological research, there are often assumptions about the conditions that children expect to encounter during their development. These assumptions shape prevailing ideas about the experiences that children are capable of adjusting to, and whether their responses are viewed as impairments or adaptations. Specifically, the expected childhood is often depicted as nurturing and safe, and characterized by high levels of caregiver investment. Here, we synthesize evidence from history, anthropology, and primatology to challenge this view. We integrate the findings of systematic reviews, meta-analyses, and cross-cultural investigations on three forms of threat (infanticide, violent conflict, and predation) and three forms of deprivation (social, cognitive, and nutritional) that children have faced throughout human evolution. Our results show that mean levels of threat and deprivation were higher than is typical in industrialized societies, and that our species has experienced much variation in the levels of these adversities across space and time. These conditions likely favored a high degree of phenotypic plasticity, or the ability to tailor development to different conditions. This body of evidence has implications for recognizing developmental adaptations to adversity, for cultural variation in responses to adverse experiences, and for definitions of adversity and deprivation as deviation from the expected human childhood.
Association of atrial septal defect and Brugada syndrome in a young woman
Authors: Tsuchihashi Tomoya , Kamada Masahiro , Nakano Yukiko
Published: December 2021

We report a 25-year-old woman who was diagnosed with atrial septal defect (ASD). An ECG showed only first-degree atrioventricular block and incomplete right bundle branch block. One day after the percutaneous ASD closure, she had a slight fever and an ECG showed a type 1 Brugada pattern. ECG characteristics of ASD are similar to those of a Brugada ECG. This case is rare combination of Brugada syndrome with ASD.
Probing the Miscibility Gap of the Pt–Pd Binary System by Atom Probe Tomography
Authors: Lee Yoonhee , Stender Patrick , Eich Sebastian Manuel , Schmitz Guido
Published: December 2021

To solve the uncertainty of the platinum (Pt)–palladium (Pd) phase diagram, especially the existence of a suggested miscibility gap, atom probe tomography (APT) was used to determine the time evolution of the composition after heat treatment. Due to the extraordinarily slow diffusion in the temperature range of the controversial phase separation, the investigated volume was limited to nano-sized multiple layers deposited by ion beam sputtering (IBS). The evaporated volume was reconstructed from the obtained datasets and the respective diffusion coefficients were determined using the Fourier series solution of the diffusion equation. Beginning with pure Pt and Pd layers annealed at 673, 773, 873, and 973 K, the mixing appears to be purely diffusion controlled in the chosen annealing times, but the state of complete mixing was still not observed. Therefore, extended isothermal annealing sequences at 673 and 773 K with pre-alloyed layers have been carried out. They clearly suggest complete mixing even at the lowest investigated temperatures.
Field-resolved high-order sub-cycle nonlinearities in a terahertz semiconductor laser
Authors: Riepl J. , Raab J. , Abajyan P. , Nong H. , Freeman J. R. , Li L. H. , Linfield E. H. , Davies A. G. , Wacker A. , Albes T. , Jirauschek C. , Lange C. , Dhillon S. S. , Huber R.
Published: December 2021

The exploitation of ultrafast electron dynamics in quantum cascade lasers (QCLs) holds enormous potential for intense, compact mode-locked terahertz (THz) sources, squeezed THz light, frequency mixers, and comb-based metrology systems. Yet the important sub-cycle dynamics have been notoriously difficult to access in operational THz QCLs. Here, we employ high-field THz pulses to perform the first ultrafast two-dimensional spectroscopy of a free-running THz QCL. Strong incoherent and coherent nonlinearities up to eight-wave mixing are detected below and above the laser threshold. These data not only reveal extremely short gain recovery times of 2 ps at the laser threshold, they also reflect the nonlinear polarization dynamics of the QCL laser transition for the first time, where we quantify the corresponding dephasing times between 0.9 and 1.5 ps with increasing bias currents. A density-matrix approach reproducing the emergence of all nonlinearities and their ultrafast evolution, simultaneously, allows us to map the coherently induced trajectory of the Bloch vector. The observed high-order multi-wave mixing nonlinearities benefit from resonant enhancement in the absence of absorption losses and bear potential for a number of future applications, ranging from efficient intracavity frequency conversion, mode proliferation to passive mode locking.
Insights into the post-translational modification and its emerging role in shaping the tumor microenvironment
Authors: Li Wen , Li Feifei , Zhang Xia , Lin Hui-Kuan , Xu Chuan
Published: December 2021

More and more in-depth studies have revealed that the occurrence and development of tumors depend on gene mutation and tumor heterogeneity. The most important manifestation of tumor heterogeneity is the dynamic change of tumor microenvironment (TME) heterogeneity. This depends not only on the tumor cells themselves in the microenvironment where the infiltrating immune cells and matrix together forming an antitumor and/or pro-tumor network. TME has resulted in novel therapeutic interventions as a place beyond tumor beds. The malignant cancer cells, tumor infiltrate immune cells, angiogenic vascular cells, lymphatic endothelial cells, cancer-associated fibroblastic cells, and the released factors including intracellular metabolites, hormonal signals and inflammatory mediators all contribute actively to cancer progression. Protein post-translational modification (PTM) is often regarded as a degradative mechanism in protein destruction or turnover to maintain physiological homeostasis. Advances in quantitative transcriptomics, proteomics, and nuclease-based gene editing are now paving the global ways for exploring PTMs. In this review, we focus on recent developments in the PTM area and speculate on their importance as a critical functional readout for the regulation of TME. A wealth of information has been emerging to prove useful in the search for conventional therapies and the development of global therapeutic strategies.
Signal pathways of melanoma and targeted therapy
Authors: Guo Weinan , Wang Huina , Li Chunying
Published: December 2021

Melanoma is the most lethal skin cancer that originates from the malignant transformation of melanocytes. Although melanoma has long been regarded as a cancerous malignancy with few therapeutic options, increased biological understanding and unprecedented innovations in therapies targeting mutated driver genes and immune checkpoints have substantially improved the prognosis of patients. However, the low response rate and inevitable occurrence of resistance to currently available targeted therapies have posed the obstacle in the path of melanoma management to obtain further amelioration. Therefore, it is necessary to understand the mechanisms underlying melanoma pathogenesis more comprehensively, which might lead to more substantial progress in therapeutic approaches and expand clinical options for melanoma therapy. In this review, we firstly make a brief introduction to melanoma epidemiology, clinical subtypes, risk factors, and current therapies. Then, the signal pathways orchestrating melanoma pathogenesis, including genetic mutations, key transcriptional regulators, epigenetic dysregulations, metabolic reprogramming, crucial metastasis-related signals, tumor-promoting inflammatory pathways, and pro-angiogenic factors, have been systemically reviewed and discussed. Subsequently, we outline current progresses in therapies targeting mutated driver genes and immune checkpoints, as well as the mechanisms underlying the treatment resistance. Finally, the prospects and challenges in the development of melanoma therapy, especially immunotherapy and related ongoing clinical trials, are summarized and discussed.
MAP4K4 mediates the SOX6-induced autophagy and reduces the chemosensitivity of cervical cancer
Authors: Huang Hongxin , Han Qin , Zheng Han , Liu Mingchen , Shi Shu , Zhang Ting , Yang Xingwen , Li Zhongqing , Xu Qiang , Guo Hongyan , Lu Fengmin , Wang Jie
Published: December 2021

There are nearly 40% of cervical cancer patients showing poor response to neoadjuvant chemotherapy that can be induced by autophagy, however, the underlying mechanism has not yet been fully clarified. We previously found thatSex-determining region of Y-related high-mobility-group box 6(SOX6), a tumor suppressor gene or oncogene in several cancers, could induce autophagy in cervical cancer. Accordingly, this study aims to investigate the mechanism of SOX6-induced autophagy and its potential significance in the platinum-based chemotherapy of cervical cancer. Firstly, we found that SOX6 could promote autophagy in cervical cancer cells depending on its HMG domain.Mitogen-activated protein kinase kinase kinase kinase-4(MAP4K4) gene was identified as the direct target gene of SOX6, which was transcriptionally upregulated by binding the HMG domain of SOX6 protein to its double-binding sites withinMAP4K4gene promoter. MAP4K4 mediated the SOX6-induced autophagy through inhibiting PI3K-Akt-mTOR pathway and activating MAPK/ERK pathway. Further, the sensitivity of cervical cancer cells to cisplatin chemotherapy could be reduced by the SOX6-induced autophagy in vitro and in vivo, while such a phenomenon could be turned over by autophagy-specific inhibitor and MAP4K4 inhibitor, respectively. Moreover, cisplatin itself could promote the expression of endogenous SOX6 and subsequently the MAP4K4-mediated autophagy in cervical cancer cells, which might in turn reduce the sensitivity of these cells to cisplatin treatment. These findings uncovered the underlying mechanism and potential significance of SOX6-induced autophagy, and shed new light on the usage of MAP4K4 inhibitor or autophagy-specific inhibitor for sensitizing cervical cancer cells to the platinum-based chemotherapy.
NLRP3 inflammasome promoted the malignant progression of prostate cancer via the activation of caspase-1
Authors: Xu Zheng , Wang Hao , Qin Zhiqiang , Zhao Feng , Zhou Liuhua , Xu Luwei , Jia Ruipeng
Published: December 2021

It is widely accepted that inflammation is an important risk for the development of prostate cancer (PCa). The objective of this study was designed to investigate the potential molecular mechanism of NLR family, pyrin domain-containing protein 3 (NLRP3) inflammasome in the malignant progression of PCa. The expression level of NLRP3 was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization. The effects of NLRP3 in the development of PCa by applying gain- and loss-of-function assays in LNCaP and PC3 cell lines were detected by CCK-8, TUNEL, and Transwell migration assays. The underlying mechanism of NLRP3 and caspase-1 in PCa was examined by the rescue experiments, western blotting, and qRT-PCR assays. In addition, the promoting effect of NLRP3 inflammasome was performed with an animal subcutaneous tumorigenesis experiment in vivo. The upregulation of NLRP3 was confirmed in PCa tissues and cell lines. Functionally, using CCK-8, TUNEL, and Transwell migration assays, these results showed that activation of NLRP3/caspase-1 inflammasome by LPS + ATP could enhance the ability of proliferation and migration; and decrease the apoptosis of LNCaP and PC3 cell lines. Western blotting assay showed that the activation of caspase-1 would increase after the stimulation of NLRP3 inflammasome by LPS + ATP. Moreover, the overexpression of NLRP3 promoted, while the knockdown of NLRP3 inhibited the malignant progression in PCa cell lines by positively regulating caspase-1. In addition, the rescue experiments revealed the association among NLRP3 and caspase-1, which showed that the overexpression vectors/inhibitors of caspase-1 could reverse the effect of knockdown/overexpression of NLRP3 in PCa cell lines in vitro. Finally, In in vivo experiment, the suppression of NLRP3 knockdown impaired tumor growth of PCa. Collectively, these results indicated that NLRP3 inflammasome played a vital role in promoting the malignant progression of PCa via the activation of caspase-1. Together, our findings provided insight into the mechanisms of NLRP3/caspase-1 inflammasome and revealed an alternative and potential target for the clinical diagnosis and treatment of PCa.
Enhancement of superexchange due to synergetic breathing and hopping in corner-sharing cuprates
Authors: Bogdanov Nikolay A. , Li Manni Giovanni , Sharma Sandeep , Gunnarsson Olle , Alavi Ali
Published: December 2021

Cuprates with corner-sharing CuO4plaquettes have received much attention owing to the discoveries of high-temperature superconductivity and exotic states where spin and charge or spin and orbital degrees of freedom are separated. In these systems spins are strongly coupled antiferromagnetically via superexchange mechanisms, with high nearest-neighbour coupling varying among different compounds. The electronic properties of cuprates are also known to be highly sensitive to the presence, distance and displacement of apical oxygens perpendicular to the CuO2planes. Here we present ab initio quantum chemistry calculations of the nearest-neighbour superexchange antiferromagnetic (AF) couplingJof two cuprates, Sr2CuO3and La2CuO4. The former lacks apical oxygens, whilst the latter contain two apical oxygens per CuO2unit completing a distorted octahedral environment around each Cu atom. Good agreement is obtained with experimental estimates for both systems. Analysis of the correlated wavefunctions together with extended superexchange models shows that there is an important synergetic effect of the Coulomb interaction and the O–Cu hopping, namely a correlated breathing-enhanced hopping mechanism. This is a new ingredient in superexchange models. Suppression of this mechanism leads to drastic reduction in the AF coupling, indicating that it is of primary importance in generating the strong interactions. We also find thatJincreases substantially as the distance between Cu and apical O is increased.
Validation and application of a novel in vivo cervical spine kinematics analysis technique
Authors: Wan Zongmiao , Wang Wenjin , Li Chao , Li Junjie , Lin Jinpeng , Tian Fei , Zhu Ting , Wu Danni , Guo Luqi , Wang Shaobai
Published: December 2021

To validate the accuracy of Cone beam computed tomography (CBCT) cervical spine modeling with three dimensional (3D)-3D registration for in vivo measurements of cervical spine kinematics. CBCT model accuracy was validated by superimposition with computed tomography (CT) models in 10 healthy young adults, and then cervical vertebrae were registered in six end positions of functional movements, versus a neutral position, in 5 healthy young adults. Registration errors and six degrees of freedom (6-DOF) kinematics were calculated and reported. Relative to CT models, mean deviations of the CBCT models were < 0.6 mm. Mean registration errors between end positions and the reference neutral position were < 0.7 mm. During flexion–extension (F–E), the translation in the three directions was small, mostly < 1 mm, with coupled LB and AR both < 1°. During lateral bending (LB), the bending was distributed roughly evenly, with coupled axial rotation (AR) opposite to the LB at C1–C2, and minimal coupled F–E. During AR, most of the rotation occurred in the C1–C2 segment (29.93 ± 7.19° in left twist and 31.38 ± 8.49° in right twist) and coupled LB was observed in the direction opposite to that of the AR. Model matching demonstrated submillimeter accuracy in cervical spine kinematics data. The presently evaluated low-radiation-dose CBCT technique can be used to measure 3D spine kinematics in vivo across functional F–E, AR, and LB positions, which has been especially challenging for the upper cervical spine.