bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical evaluation of [18F] JNJ-64326067, a novel candidate PET tracer for the detection of tau pathology in Alzheimer’s disease
Authors: Schmidt Mark E. , Janssens Luc , Moechars Diederik , Rombouts Frederik J. R. , Timmers Maarten , Barret Olivier , Constantinescu Cristian C. , Madonia Jennifer , Russell David S. , Sandiego Christine M. , Kolb Hartmuth
Published: June 2020

Purpose

The accumulation of misfolded tau is a common feature of several neurodegenerative disorders, with Alzheimer’s disease (AD) being the most common. Earlier we identified JNJ-64326067, a novel isoquinoline derivative with high affinity and selectivity for tau aggregates from human AD brain. We report the dosimetry of [18F] JNJ-64326067 and results of a proof-of-concept study comparing subjects with probable Alzheimer’s disease to age-matched healthy controls.

Methods

[18F] JNJ-64326067 PET scans were acquired for 90 min and then from 120 to 180 min in 5 participants with [18F]-florbetapir PET amyloid positive probable AD (73 ± 9 years) and 5 [18F]-florbetapir PET amyloid negative healthy controls (71 ± 7 years). Whole-body [18F] JNJ-64326067 PET CT scans were acquired in six healthy subjects for 5.5 h in 3 scanning sessions. Brain PET scans were visually reviewed. Regional quantification included kinetic analysis of distribution volume ration (DVR) estimated by Logan graphical analysis over the entire scan and static analysis of SUVr in late frames. Both methods used ventral cerebellar cortex as a reference region.

Results

One of the healthy controls had focal areas of PET signal in occipital and parietal cortex underlying the site of a gunshot injury as an adolescent; the other four healthy subjects had no tau brain signal. Four of the 5 AD participants had visually apparent retention of [18F] JNJ-64326067 in relevant cortical regions. One of the AD subjects was visually negative. Cortical signal in visually positive subjects approached steady state by 120 min. Temporal and frontal cortical SUVr/DVR values in visually positive AD subjects ranged from 1.21 to 3.09/1.2 to 2.18 and from 0.92 to 1.28/0.91 to 1.16 in healthy controls. Whole-body effective dose was estimated to be 0.0257 mSv/MBq for females and 0.0254 mSv/MBq for males.

Conclusions

[18F] JNJ-64326067 could be useful for detection and quantitation of tau aggregates.
Presenting symptoms in children with neurofibromatosis type 2
Authors: Gugel Isabel , Grimm Florian , Teuber Christian , Zipfel Julian , Tatagiba Marcos , Mautner Victor-Felix , Schuhmann Martin Ulrich , Kluwe Lan
Published: June 2020

Purpose

The hallmark of neurofibromatosis type 2 (NF2) is the presence of bilateral vestibular schwannomas (VS) which however have not yet developed or grown to large size in children and young adolescents. Therefore, early diagnosis in pediatric patients without family history of NF2 has to be made by signs and symptoms not related to VS which will be reviewed in this study.

Methods

A total of 70 children diagnosed for NF2 at an age of < 18 years were identified from our patient cohort. Age and symptoms, signs and pathology at symptom onset, age at NF2 diagnosis and symptoms leading to diagnosis as well as genetic findings were retrospectively reviewed.

Results

The average age at symptom/sign onset was 8 ± 6 (range 0–17) years and 11 ± 5 (range 1–17) years at time of diagnosis. Fifteen children had a positive family history and were diagnosed upon additional clinical symptoms. The most frequent first presenting symptom/signs were ophthalmological abnormalities (49%), followed by cutaneous features (40%), non-VS-related neurological deficits (33%), and symptoms attributable to VS (21%). VS were not only the most common symptomatic neoplasm but also the most frequent pathological evidence for the diagnosis (72%). In 42 patients with available genetic testing results, pathogenic mutations were most frequently identified (n = 27).

Conclusion

The presenting symptoms in NF2 children appear “unspecific” or less specific for classical NF2 compared with adult NF2 patients, posing a challenge particularly for cases without family history. In children, ophthalmological and cutaneous features should raise clinical suspicion for NF2 and referral to an NF2 specialized center is recommended.
Effects of chronic consumption of specific fruit (berries, citrus and cherries) on CVD risk factors: a systematic review and meta-analysis of randomised controlled trials
Authors: Wang Yueyue , Gallegos Jose Lara , Haskell-Ramsay Crystal , Lodge John K.
Published: June 2020

Purpose

This review aims to compare the magnitude of the effects of chronic consumption of fruits; specifically berries, citrus and cherries on cardiovascular disease (CVD) risk factors.

Methods

PubMed, Web of Science, Scopus, and psycARTICLES were searched from inception until January 2020. Forty-five chronic (≥ 1 week) randomised controlled trials assessing CVD risk factors including endothelial (dys)function, blood pressure (BP), blood lipids and inflammatory biomarkers were included.

Results

Investigated interventions reported improvements in endothelial function (n = 8), inflammatory biomarkers and lipid status (n = 14), and BP (n = 10). Berries including juice of barberry, cranberry, grape, pomegranate, powder of blueberry, grape, raspberry and freeze-dried strawberry significantly reduced SBP by 3.68 mmHg (95% CI − 6.79 to − 0.58; P = 0.02) and DBP by 1.52 mmHg (95% CI − 2.87 to − 0.18, P = 0.04). In subgroup analysis, these associations were limited to cranberry juice (SBP by 1.52 mmHg [95% CI − 2.97 to − 0.07; P = 0.05], DBP by 1.78 mmHg [95% CI − 3.43 to − 0.12, P = 0.04] and cherry juice (SBP by 3.11 mmHg [95% CI − 4.06 to − 2.15; P = 0.02]). Berries also significantly elevated sVCAM-1 levels by 14.57 ng/mL (85% CI 4.22 to 24.93; P = 0.02).

Conclusion

These findings suggest that supplementing cranberry or cherry juice might contribute to an improvement in blood pressure. No other significant improvements were observed for other specified fruits. More research is warranted comparing different classes of fruit and exploring the importance of fruit processing on their cardiovascular-protective effects.
Surface charge density and diffuse layer properties of highly defined 2:1 layered silicate platelets
Authors: Kuznetsov Volodymyr , Ottermann Katharina , Helfricht Nicolas , Kunz Daniel , Loch Patrick , Kalo Hussein , Breu Josef , Papastavrou Georg
Published: June 2020

Clays are not only ubiquitous in nature, but they are also used in huge quantities in a broad range of industrial applications, such as thixotropic drilling fluids, ore pelletizers, waste disposal sealants, or fillers in polymer nanocomposites. In order to model environmental processes or to design new materials on a rational base, it is of prime importance to determine and possibly modify the interfacial properties of clay platelets at the solid/electrolyte interface. In this context, the fundamental question rises how far the stoichiometric interlayer charges as determined by the composition of the silicate layer correlates with the diffuse double-layer properties. Here, this question is addressed by means of a series of purposely synthesized sodium 2:1 layered silicates with defined composition and hence interlayer charge densities, respectively. Platelets of layered silicates of large enough diameter to perform AFM colloidal probe measurements were produced by melt synthesis. For comparison also, a natural muscovite mica has been included in this study. The diffuse layer properties in electrolyte solution have been determined by direct force measurements using the colloidal probe AFM technique and by electrokinetic measurements, respectively. We find that the diffuse layer potential decreases with increasing interlayer charge of the 2:1 layered silicates. This counterintuitive finding is attributed to ion adsorption and was further corroborated by determining the quantitative adsorption of polyelectrolytes, namely poly(amidoamine) dendrimers.
Prion propagation estimated from brain diffusion MRI is subtype dependent in sporadic Creutzfeldt–Jakob disease
Authors: Pascuzzo Riccardo , Oxtoby Neil P. , Young Alexandra L. , Blevins Janis , Castelli Gianmarco , Garbarino Sara , Cohen Mark L. , Schonberger Lawrence B. , Gambetti Pierluigi , Appleby Brian S. , Alexander Daniel C. , Bizzi Alberto
Published: June 2020

Sporadic Creutzfeldt–Jakob disease (sCJD) is a transmissible brain proteinopathy. Five main clinicopathological subtypes (sCJD-MM(V)1, -MM(V)2C, -MV2K, -VV1, and -VV2) are currently distinguished. Histopathological evidence suggests that the localisation of prion aggregates and spongiform lesions varies among subtypes. Establishing whether there is an initial site with detectable imaging abnormalities (epicentre) and an order of lesion propagation would be informative for disease early diagnosis, patient staging, management and recruitment in clinical trials. Diffusion magnetic resonance imaging (MRI) is the most-used and most-sensitive test to detect spongiform degeneration. This study was designed to identify, in vivo and for the first time, subtype-dependent epicentre and lesion propagation in the brain using diffusion-weighted images (DWI), in the largest known cross-sectional dataset of autopsy-proven subjects with sCJD. We estimate lesion propagation by cross-sectional DWI using event-based modelling, a well-established data-driven technique. DWI abnormalities of 594 autopsy-diagnosed subjects (448 patients with sCJD) were scored in 12 brain regions by 1 neuroradiologist blind to the diagnosis. We used the event-based model to reconstruct sequential orderings of lesion propagation in each of five pure subtypes. Follow-up data from 151 patients validated the estimated sequences. Results showed that epicentre and ordering of lesion propagation are subtype specific. The two most common subtypes (-MM1 and -VV2) showed opposite ordering of DWI abnormality appearance: from the neocortex to subcortical regions, and vice versa, respectively. The precuneus was the most likely epicentre also in -MM2 and -VV1 although at variance with -MM1, abnormal signal was also detected early in cingulate and insular cortices. The caudal-rostral sequence of lesion propagation that characterises -VV2 was replicated in -MV2K. Combined, these data-driven models provide unprecedented dynamic insights into subtype-specific epicentre at onset and propagation of the pathologic process, which may also enhance early diagnosis and enable disease staging in sCJD.
Peroxynitrite induced signaling pathways in plant response to non-proteinogenic amino acids
Authors: Staszek Pawel , Gniazdowska Agnieszka
Published: June 2020

Main conclusion

Nitro/oxidative modifications of proteins and RNA nitration resulted from altered peroxynitrite generation are elements of the indirect mode of action of canavanine andmeta-tyrosine in plants

Environmental conditions and stresses, including supplementation with toxic compounds, are known to impair reactive oxygen (ROS) and reactive nitrogen species (RNS) homeostasis, leading to modification in production of oxidized and nitrated derivatives. The role of nitrated and/or oxidized biotargets differs depending on the stress factors and developmental stage of plants. Canavanine (CAN) andmeta-tyrosine (m-Tyr) are non-proteinogenic amino acids (NPAAs). CAN, the structural analog of arginine, is found mostly in seeds of Fabaceae species, as a storage form of nitrogen. In mammalian cells, CAN is used as an anticancer agent due to its inhibitory action on nitric oxide synthesis.m-Tyr is a structural analogue of phenylalanine and an allelochemical found in root exudates of fescues. In animals,m-Tyr is recognized as a marker of oxidative stress. Supplementation of plants with CAN orm-Tyr modify ROS and RNS metabolism. Over the last few years of our research, we have collected the complex data on ROS and RNS metabolism in tomato (Solanum lycopersicumL.) plants exposed to CAN orm-Tyr. In addition, we have shown the level of nitrated RNA (8-Nitro-guanine) in roots of seedlings, stressed by the tested NPAAs. In this review, we describe the model of CAN andm-Tyr mode of action in plants based on modifications of signaling pathways induced by ROS/RNS with a special focus on peroxynitrite induced RNA and protein modifications.
The visual white matter connecting human area prostriata and the thalamus is retinotopically organized
Authors: Kurzawski Jan W. , Mikellidou Kyriaki , Morrone Maria Concetta , Pestilli Franco
Published: June 2020

The human visual system is capable of processing visual information from fovea to the far peripheral visual field. Recent fMRI studies have shown a full and detailed retinotopic map in area prostriata, located ventro-dorsally and anterior to the calcarine sulcus along the parieto-occipital sulcus with strong preference for peripheral and wide-field stimulation. Here, we report the anatomical pattern of white matter connections between area prostriata and the thalamus encompassing the lateral geniculate nucleus (LGN). To this end, we developed and utilized an automated pipeline comprising a series of Apps that run openly on the cloud computing platform brainlife.io to analyse 139 subjects of the Human Connectome Project (HCP). We observe a continuous and extended bundle of white matter fibers from which two subcomponents can be extracted: one passing ventrally parallel to the optic radiations (OR) and another passing dorsally circumventing the lateral ventricle. Interestingly, the loop travelling dorsally connects the thalamus with the central visual field representation of prostriata located anteriorly, while the other loop travelling more ventrally connects the LGN with the more peripheral visual field representation located posteriorly. We then analyse an additional cohort of 10 HCP subjects using a manual plane extraction method outside brainlife.io to study the relationship between the two extracted white matter subcomponents and eccentricity, myelin and cortical thickness gradients within prostriata. Our results are consistent with a retinotopic segregation recently demonstrated in the OR, connecting the LGN and V1 in humans and reveal for the first time a retinotopic segregation regarding the trajectory of a fiber bundle between the thalamus and an associative visual area.
Morphological and molecular identification of ixodid tick species (Acari: Ixodidae) infesting cattle in Uganda
Authors: Balinandi Stephen , Chitimia-Dobler Lidia , Grandi Giulio , Nakayiki Teddy , Kabasa William , Bbira Johnson , Lutwama Julius J. , Bakkes Deon K. , Malmberg Maja , Mugisha Lawrence
Published: June 2020

In Uganda, the role of ticks in zoonotic disease transmission is not well described, partly, due to limited available information on tick diversity. This study aimed to identify the tick species that infest cattle. Between September and November 2017, ticks (n = 4362) were collected from 5 districts across Uganda (Kasese, Hoima, Gulu, Soroti, and Moroto) and identified morphologically at Uganda Virus Research Institute. Morphological and genetic validation was performed in Germany on representative identified specimens and on all unidentified ticks. Ticks were belonging to 15 species: 8Rhipicephalusspecies (Rhipicephalus appendiculatus,Rhipicephalus evertsi evertsi,Rhipicephalus microplus,Rhipicephalus decoloratus,Rhipicephalus afranicus,Rhipicephalus pulchellus,Rhipicephalus simus, andRhipicephalus sanguineustropical lineage); 5Amblyommaspecies (Amblyomma lepidum,Amblyomma variegatum,Amblyomma cohaerens,Amblyomma gemma, andAmblyomma paulopunctatum); and 2Hyalommaspecies (Hyalomma rufipesandHyalomma truncatum). The most common species wereR. appendiculatus(51.8%),A. lepidum(21.0%),A. variegatum(14.3%),R. evertsi evertsi(8.2%), andR. decoloratus(2.4%). R. afranicusis a new species recently described in South Africa and we report its presence in Uganda for the first time. The sequences ofR. afranicuswere 2.4% divergent from those obtained in Southern Africa. We confirm the presence of the invasiveR. microplusin two districts (Soroti and Gulu). Species diversity was highest in Moroto district (p = 0.004) and geographical predominance by specific ticks was observed (p = 0.001). The study expands the knowledge on tick fauna in Uganda and demonstrates that multiple tick species with potential to transmit several tick-borne diseases including zoonotic pathogens are infesting cattle.
Brennerversuchseinrichtung
Authors: Spijker Christoph , Doschek-Held Klaus , Raupenstrauch Harald
Published: June 2020

Derzeit befindet sich am Lehrstuhl für Thermoprozesstechnik der Montanuniversität Leoben eine Brennerversuchseinrichtung in Bau. Diese ist in der Lage, industrielle Brenner mit einer Leistung von bis zu 1 MW im Erdgas-Luftbetrieb beziehungsweise 1,5 MW im Erdgas-Sauerstoffbetrieb zu vermessen. Des Weiteren besteht die Möglichkeit der Zumischung von alternativen Gasen durch Flaschenbündeln. Neben der Messung mit Lanzen und Absaugpyrometern besteht die Möglichkeit – in Kooperation mit dem Lehrstuhl für Verfahrenstechnik des industriellen Umweltschutzes – Strömungs- und Turbulenzfelder sowie chemische Konzentrationen über Lasermessverfahren im Raum zu erfassen. Parallel zu der Brennerversuchseinrichtung entsteht ein digitales Abbild dieser. Hierbei liegt der Fokus auf der Brenneroptimierung hinsichtlich Emissionen, Flammbild und Effizienz, welche durch ein Simulationskonzept und unter Verwendung von Computational Fluid Dynamics (CFD) beziehungsweise eigens entwickelter Modelle berechnet werden. Ein zentraler Punkt hierbei sind der am Lehrstuhl für Thermoprozesstechnik entwickelten NOX Postprocessoren, welche eine schnelle und präzise Aussage über die Bildung von Stickoxiden ermöglichen.
Traditional serrated adenoma has two distinct genetic pathways for molecular tumorigenesis with potential neoplastic progression
Authors: Tanaka Yoshihito , Eizuka Makoto , Uesugi Noriyuki , Kawasaki Keisuke , Yamano Hiroo , Suzuki Hiromu , Matsumoto Takayuki , Sugai Tamotsu
Published: June 2020

Background

Recent studies have shown that traditional serrated adenoma (TSA) can be classified into BRAF and KRAS subtypes. Here, we examined the clinicopathological and molecular findings of 73 TSAs.

Materials and methods

TSAs were subclassified into BRAF type (46 cases, type A) and KRAS type (27 cases, type B) and divided into polyp head (TSA component) and base (precursor component [PC]) to identify pathological and molecular differences between the two components. BRAF and KRAS mutations, microsatellite instability (MSI), and DNA methylation status of the TSA component and PC were analyzed. In addition, immunohistochemical expressions of annexin A10, MUC2, MUC5AC, MUC6, and CD10 were also examined. Finally, we compared endoscopic findings with histological features.

Results

We classified type As into 31 type A1s with mutation of the corresponding PC (42.5%) and 15 type A2s without mutation of the PC (20.5%). None of the corresponding PCs without KRAS mutation were observed in type Bs. MSI was not detected in the TSAs examined. There were significant differences in the frequency of annexin A10 and MUC5AC expression between the three subtypes. Furthermore, we compared the TSA component with the corresponding PC to identify the progression mechanism between the two components. Methylation status played an important role in the progression of type A1 from the corresponding PC, unlike type A2 and type B. Finally, specific endoscopic findings were well correlated with distinct histological findings.

Conclusion

TSAs were heterogeneous tumors with two or three pathways to neoplastic progression.
Discrete optimization methods for group model selection in compressed sensing
Authors: Bah Bubacarr , Kurtz Jannis , Schaudt Oliver
Published: June 2020

In this article we study the problem of signal recovery for group models. More precisely for a given set of groups, each containing a small subset of indices, and for given linear sketches of the true signal vector which is known to be group-sparse in the sense that its support is contained in the union of a small number of these groups, we study algorithms which successfully recover the true signal just by the knowledge of its linear sketches. We derive model projection complexity results and algorithms for more general group models than the state-of-the-art. We consider two versions of the classical iterative hard thresholding algorithm (IHT). The classical version iteratively calculates the exact projection of a vector onto the group model, while the approximate version (AM-IHT) uses a head- and a tail-approximation iteratively. We apply both variants to group models and analyse the two cases where the sensing matrix is a Gaussian matrix and a model expander matrix. To solve the exact projection problem on the group model, which is known to be equivalent to the maximum weight coverage problem, we use discrete optimization methods based on dynamic programming and Benders’ decomposition. The head- and tail-approximations are derived by a classical greedy-method and LP-rounding, respectively.
Rational modification of the carbon metabolism of Corynebacterium glutamicum to enhance l-leucine production
Authors: Wang Ying-Yu , Shi Ke , Chen Peidong , Zhang Feng , Xu Jian-Zhong , Zhang Wei-Guo
Published: June 2020

l-Leucine is an essential amino acid that has wide and expanding applications in the industry. It is currently fast-growing market demand that provides a powerful impetus to further increase its bioconversion productivity and production stability. In this study, we rationally engineered the metabolic flux from pyruvate to l-leucine synthesis in Corynebacterium glutamicum to enhance both pyruvate availability and l-leucine synthesis. First, the pyc (encoding pyruvate carboxylase) and avtA (encoding alanine-valine aminotransferase) genes were deleted to weaken the metabolic flux of the tricarboxylic acid cycle and reduce the competitive consumption of pyruvate. Next, the transcriptional level of the alaT gene (encoding alanine aminotransferase) was down regulated by inserting a terminator to balance l-leucine production and cell growth. Subsequently, the genes involved in l-leucine biosynthesis were overexpressed by replacing the native promoters PleuA and PilvBNC of the leuA gene and ilvBNC operon, respectively, with the promoter Ptuf of eftu (encoding elongation factor Tu) and using a shuttle expression vector. The resulting strain WL-14 produced 28.47 ± 0.36 g/L l-leucine in shake flask fermentation.
Identification of Citruses from Montenegro Based on Microsatellite Clustering Analyses
Authors: Bitz Lidija , Malidzan Slavojka , Stajner Natasa , Tenhola-Roininen Teija , Javornik Branka
Published: June 2020

A set of 32 citrus genotypes were selected from Montenegro collection and analyzed by the use of 11 microsatellite markers. Analyses harvested 72 different alleles having 6.5 alleles per locus and discovered presence of 23 unique genotypes. Distance analysis and model-based clustering revealed both the presence of 4 groups: satsuma (Citrus unshiuMarc.) mandarins, clementine (Citrus reticulata) mandarins, sweet oranges (Citrus × sinensis) and lemons (Citrus limon). Distance based clustering enabled the differentiation between red and yellow flashed fruits due to the presence of allele 158 on the locus AC01 in blood oranges. Specific goal of the study was to clarify the identity of 3 local citrus genotypes through observing their relationships within well-established clustering with the rest of genotypes being known citruses. Local orange ‘Domaca Pomorandza’ grouped with other sweet oranges but could not be differentiated from ‘Navelina’ and ‘Skagss Bonanza Navel’. ‘Gorka Pomorandza’ had unique fingerprint and showed to be sour orange. Local lemon ‘Mjesecar’ showed to may be belonging to the Femminello group of lemons. Genetic characterization of local genotypes will serve for cultivar recognition and their future improvement.
Assessing the protective role of alpine forests against rockfall at regional scale
Authors: Scheidl Christian , Heiser Micha , Vospernik Sonja , Lauss Elisabeth , Perzl Frank , Kofler Andreas , Kleemayr Karl , Bettella Francesco , Lingua Emanuele , Garbarino Matteo , Skudnik Mitja , Trappmann Daniel , Berger Frederic
Published: June 2020

Worldwide, mountain forests represent a significant factor in reducing rockfall risk over long periods of time on large potential disposition areas. While the economic value of technical protection measures against rockfall can be clearly determined and their benefits indicated, there is no general consensus on the quantification of the protective effect of forests. Experience shows that wherever there is forest, the implementation of technical measures to reduce risk of rockfall might often be dispensable or cheaper, and large deforestations (e.g. after windthrows, forest fires, clear-cuts) often show an increased incidence of rockfall events. This study focussed on how the protective effect of a forest against rockfall can be quantified on an alpine transregional scale. We therefore estimated the runout length, in terms of the angle of reach, of 700 individual rockfall trajectories from 39 release areas from Austria, Germany, Italy and Slovenia. All recorded rockfall events passed through forests which were classified either as coppice forests or, according to the CORINE classification of land cover, as mixed, coniferous or broadleaved dominated high forest stands. For each individual rockfall trajectory, we measured the forest structural parameters stem number, basal area, top height, ratio of shrub to high forest and share of coniferous trees. To quantify the protective effect of forests on rockfall, a hazard reduction factor is introduced, defined as the ratio between an expected angle of reach without forest and the back-calculated forest-influenced angles of reach. The results show that forests significantly reduce the runout length of rockfall. The highest reduction was observed for mixed high forest stands, while the lowest hazard reduction was observed for high forest stands dominated either by coniferous or broadleaved tree species. This implies that as soon as one tree species dominates, the risk reduction factor becomes lower. Coppice forests showed the lowest variability in hazard reduction. Hazard reduction due to forests increases, on average, by 7% for an increase in the stem number by 100 stems per hectare. The proposed concept allows a global view of the effectiveness of protective forests against rockfall processes and thus enable to value forest ecosystem services for future transregional assessments on a European level. Based on our results, general cost–benefit considerations of nature-based solutions against rockfall, such as protective forests as well as first-order evaluations of rockfall hazard reduction effects of silvicultural measures within the different forest types, can be supported.
On the Challenges of Soil Phosphorus Prospections in Heterogeneous Environments—a Case Study on the Iron Age Altenburg Hillfort (Niedenstein, Hesse, Germany)
Authors: Weihrauch Christoph , Söder Ulrike
Published: June 2020

Heterogeneous environments might be considered inadequate for geoarchaeological soil phosphorus (P) prospections due to the manifold potential alterations of archaeologically relevant soil P contents. To elucidate if this assumption is correct, we conducted a case study in the heterogeneous environment of the Iron Age Altenburg hillfort near Niedenstein (Hesse, Germany). We introduce theleast influenced area(LIA) approach to deduce the native soil P contents of the local soils inductively from own soil P data. The native P contents are crucial for further data evaluation in any P prospection. Moreover, we develop two parameters to quantify and compare soil P enrichment in pedogenically heterogeneous areas: themean enrichment ratio(MER) and themaximum enrichment ratio(XER). Finally, we modify and discuss the approach of Lorch (The Science of Nature28(40/41):633–640, 1940) to interpret spatial patterns of soil P enrichment with regard to prehistoric land use. Our study shows that soil P prospections can be conducted in heterogeneous environments. Still, they require a systematic field work strategy and soil scientific support. Moreover, instead of absolute soil P contents, alternative parameters must be derived from the data to evaluate soil P enrichment adequately for a heterogeneous area. Using such alternative parameters on the basis of our data, the Iron Age Altenburg hillfort was significantly larger than formerly assumed. Only the Altenburg plateau and the directly adjacent slopes seem to have been densely covered with buildings. The neighboring areas might have been used for different purposes including agriculture, livestock grazing, and economic activities.
Metal halide-based photodetector using one-dimensional MAPbI3 micro rods
Authors: Raza Ehsan , Ahmad Zubair , Mishra Arti , Aziz Fakhra
Published: June 2020

In the present work, we report the fabrication of a photodetector using methylammonium lead iodide perovskite (MAPbI3) micro rod. Photosensitivity of the Ag/MAPbI3/Ag photodetector has been studied under various light intensities ranging from 10 to 100 mW/cm2. The MAPbI3 perovskite micro rod-based photodetector shows a high on/off ratio (4.47 × 105), and fast response & recovery times (2.7 ms, each), as compared to the photodetectors using perovskite films. This work could initiate new perspectives for perovskite micro rods to be employed in high-performance optoelectronic devices.
Global post-marketing safety surveillance of Tumor Treating Fields (TTFields) in patients with high-grade glioma in clinical practice
Authors: Shi Wenyin , Blumenthal Deborah T. , Oberheim Bush Nancy Ann , Kebir Sied , Lukas Rimas V. , Muragaki Yoshihiro , Zhu Jay-Jiguang , Glas Martin
Published: June 2020

Introduction

Tumor Treating Fields (TTFields; antimitotic treatment) delivers low-intensity, intermediate-frequency, alternating electric fields through skin-applied transducer arrays. TTFields (200 kHz) was FDA-approved in glioblastoma (GBM), based on the phase 3 EF-11 (recurrent GBM, rGBM) and EF-14 (newly diagnosed GBM, ndGBM) trials. The most common TTFields-related adverse event (AE) in both trials was array-associated skin irritation. We now report on TTFields-related AEs in the real-world, clinical practice setting.

Methods

Unsolicited, post-marketing surveillance data from TTFields-treated patients (October 2011–February 2019) were retrospectively analyzed using MedDRA v21.1 preferred terms, stratified by region (US, EMEA [Europe, Middle East, Africa], Japan), diagnosis (ndGBM, rGBM, anaplastic astrocytoma/oligodendroglioma, other brain tumors), and age (< 18 [pediatric], 18–64 [adults], ≥ 65 [elderly]; years of age).

Results

Of 11,029 patients, 53% were diagnosed with ndGBM and 39% were diagnosed with rGBM at any line of disease recurrence. Most were adults (73%), 26% were elderly, and the male-to-female ratio was ~ 2:1 (close to published ratios of typical GBM populations). The most commonly reported TTFields-related AE was array-associated skin reaction, occurring in patients with ndGBM (38%), rGBM (29%), anaplastic astrocytoma/oligodendroglioma (38%), and other brain tumors (31%); as well as 37% of pediatric, 34% of adult, and 36% of elderly patients. Most skin AEs were mild/moderate and manageable. Other TTFields-related AEs in patients with ndGBM/rGBM included under-array heat sensation (warmth; 11%, 10%, respectively) and electric sensation (tingling; 11%, 9%, respectively), and headache (7%, 6%, respectively).

Conclusions

This TTFields safety surveillance analysis in > 11,000 patients revealed no new safety concerns, with a favorable safety profile comparable with published TTFields/GBM trials. The safety profile remained consistent among subgroups, suggesting feasibility in multiple populations, including elderly patients.

Graphic abstract
Analysis of cat diet across an urbanisation gradient
Authors: Piontek Aleksandra M. , Wojtylak-Jurkiewicz Ewa , Schmidt Krzysztof , Gajda Agnieszka , Lesiak Maciej , Wierzbowska Izabela A.
Published: June 2020

The domestic cat is a widespread and abundant predator that negatively impacts a wide range of species. However, the predation activity and prey type of free-ranging cats may vary between areas with different levels urbanisation. Previous analyses of cat diet have used differing techniques to measure predation that often differ with one another. Given the variability in these methods we hypothesised that cats in rural areas will have a more diverse diet than in urban areas and their predation rate may be higher than those in the urban sites. Moreover, we hypothesized that the diet of urban cats should be highly influenced by anthropogenic food. We selected sites across a rural-to-urban gradient and used three methods of analysis to determine prey in the diet (cat stomachs, cat scats, and prey brought home). We collected 81 stomachs, 409 scats, and 337 prey items of free-roaming cats from six study sites located in southern and eastern Poland. We found seasonal and habitat related differences in prey composition. The proportion of scats and stomachs containing vertebrate varied from 17% in urban areas to 79% in one of the rural areas. Small rodents were the dominant prey category, followed by birds and soricomorphs. Anthropogenic food was found to be an important part of urban cats’ diet, but its significance decreased with a decrease in urbanisation level. Both predation rate and prey diversity were highest in rural areas. While diet analysis provided a better estimation of cat predation rate, the detailed prey examination provided better insight into less common taxa killed by the cats, such as reptiles and small mustelids. Our results contribute to the discussion about the risks associated with the activity of free ranging cats especially in areas with high conservation values.
Light source calibration for multispectral imaging in surgery
Authors: Ayala Leonardo , Seidlitz Silvia , Vemuri Anant , Wirkert Sebastian J. , Kirchner Thomas , Adler Tim J. , Engels Christina , Teber Dogu , Maier-Hein Lena
Published: June 2020

Purpose

Live intra-operative functional imaging has multiple potential clinical applications, such as localization of ischemia, assessment of organ transplantation success and perfusion monitoring. Recent research has shown that live monitoring of functional tissue properties, such as tissue oxygenation and blood volume fraction, is possible using multispectral imaging in laparoscopic surgery. While the illuminant spectrum is typically kept constant in laparoscopic surgery and can thus be estimated from preoperative calibration images, a key challenge in open surgery originates from the dynamic changes of lighting conditions.

Methods

The present paper addresses this challenge with a novel approach to light source calibration based on specular highlight analysis. It involves the acquisition of low-exposure time images serving as a basis for recovering the illuminant spectrum from pixels that contain a dominant specular reflectance component.

Results

Comprehensive in silico and in vivo experiments with a range of different light sources demonstrate that our approach enables an accurate and robust recovery of the illuminant spectrum in the field of view of the camera, which results in reduced errors with respect to the estimation of functional tissue properties. Our approach further outperforms state-of-the-art methods proposed in the field of computer vision.

Conclusion

Our results suggest that low-exposure multispectral images are well suited for light source calibration via specular highlight analysis. This work thus provides an important first step toward live functional imaging in open surgery.
Cancer Risk After Bariatric Surgery in a Cohort Study from the Five Nordic Countries
Authors: Tao Wenjing , Santoni Giola , von Euler-Chelpin My , Ljung Rickard , Lynge Elsebeth , Pukkala Eero , Ness-Jensen Eivind , Romundstad Pål , Tryggvadottir Laufey , Lagergren Jesper
Published: June 2020

Purpose

Obesity increases the risk of several cancers, but the influence of bariatric surgery on the risk of individual obesity-related cancers is unclear. This study aimed to assess the impact of bariatric surgery on cancer risk in a multi-national setting.

Materials and Methods

This cohort study included all adults with an obesity diagnosis identified from national patient registries in all Nordic countries (Denmark, Finland, Iceland, Norway and Sweden) from 1980 to 2012. Cancer risk in bariatric surgery patients was compared with non-operated patients with obesity. Multivariable Cox regression provided adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Age, sex, calendar year, country, length of follow-up, diabetes, chronic obstructive pulmonary disease and alcohol-related diseases were evaluated as confounders.

Results

Among 482,572 participants with obesity, 49,096 underwent bariatric surgery. Bariatric surgery was followed by a decreased overall cancer risk in women (HR 0.86, 95% CI 0.80–0.92), but not in men (HR 0.98, 95% CI 0.95–1.01). The risk reduction was observed only within the first five post-operative years. Among specific tumours, HRs decreased for breast cancer (HR 0.81, 95% CI 0.69–0.95), endometrial cancer (HR 0.69, 95% CI 0.56–0.84) and non-Hodgkin lymphoma (HR 0.64, 95% CI 0.42–0.97) in female bariatric surgery patients, while the risk of kidney cancer increased in both sexes (HR 1.44, 95% CI 1.13–1.84).

Conclusion

Bariatric surgery may decrease overall cancer risk in women within the first five years after surgery. This decrease may be explained by a decreased risk of breast and endometrial cancer and non-Hodgkin lymphoma in women.
Pre-operative Obesity-Associated Hyperandrogenemia in Women and Hypogonadism in Men Have No Impact on Weight Loss Following Bariatric Surgery
Authors: Beiglböck Hannes , Fellinger Paul , Ranzenberger-Haider Tamara , Itariu Bianca , Prager Gerhard , Kautzky-Willer Alexandra , Krebs Michael , Wolf Peter
Published: June 2020

Background

In severe obesity, hypogonadism in men and androgen excess in women are frequently observed. Sex hormones play an important role in body composition and glucose and lipid metabolism. However, whether pre-operative gonadal dysfunction impacts weight loss after bariatric surgery is not fully known.

Methods

A total of 49 men and 104 women were included in a retrospective analysis. Anthropometric characteristics, glucose and lipid metabolism, and androgen concentrations were assessed pre-operatively and 17.9 ± 11 or 19.3 ± 12 months post-operatively in men and women. Men with (HYPOmale) and without (controls: CONmale) pre-operative hypogonadism, as well as women with (HYPERfemale) and without (controls: CONfemale) pre-operative hyperandrogenemia, were compared.

Results

In men, pre-operative hypogonadism was present in 55% and linked to a higher body mass index (BMI): HYPOmale 50 ± 6 kg/m2 vs. CONmale 44 ± 5 kg/m2, p = 0.001. Bariatric surgery results in comparable changes in BMI in HYPOmale and CONmale − 16 ± 6 kg/m2 vs. − 14 ± 5 kg/m2, p = 0.30. Weight loss reversed hypogonadism in 93%. In women, androgen excess was present in 22%, independent of pre-operative BMI: CONfemale 44 ± 7 kg/m2 vs. HYPERfemale 45 ± 7 kg/m2, p = 0.57. Changes in BMI were comparable in HYPERfemale and CONfemale after bariatric surgery − 15 ± 6 kg/m2 vs. − 15 ± 5 kg/m2, p = 0.88. Hyperandrogenemia was reversed in 61%.

Conclusions

Besides being frequently observed, hypogonadism in men and androgen excess in women have no impact on post-surgical improvements in body weight and glucose and lipid metabolism. Weight loss resulted in reversal of hypogonadism in almost all men and of hyperandrogenemia in the majority of women.
Backbone resonance assignments of the catalytic and regulatory domains of Ca2+/calmodulin-dependent protein kinase 1D
Authors: Tong Michael H. G. , Jeeves Mark , Rajesh Sundaresan , Ludwig Christian , Lenoir Marc , Kumar Jitendra , McClelland Darren M. , Berditchevski Fedor , Hubbard Julia A. , Kenyon Colin , Butterworth Sam , Knapp Stefan , Overduin Michael
Published: June 2020

The CaMK subfamily of Ser/Thr kinases are regulated by calmodulin interactions with their C-terminal regions. They are exemplified by Ca2+/calmodulin dependent protein kinase 1δ which is known as CaMK1D, CaMKIδ or CKLiK. CaMK1D mediates intracellular signalling downstream of Ca2+ influx and thereby exhibits amplifications of Ca2+signals and polymorphisms that have been implicated in breast cancer and diabetes. Here we report the backbone 1H, 13C, 15N assignments of the 38 kDa human CaMK1D protein in its free state, including both the canonical bi-lobed kinase fold as well as the autoinhibitory and calmodulin binding domains.
A censored‐Poisson model based approach to the analysis of RNA‐seq data
Authors: Chen Xing , Lai Yinglei
Published: June 2020

Background

With the recent advance of sequencing technology, the collection of RNA expression (RNA‐seq) data has been growing rapidly. RNA‐seq data are statistically count‐type measurements. Poisson distribution is a basic probability distribution for modeling count‐type data. With Poisson regression models, various experimental factors, GC content as well as alternative splicing isoforms can be flexibly considered in RNA‐seq data analysis. Due to the biochemical and technical limitations of sequencing technology, the biases among RNA‐seq data have been recognized.

Methods

In this study, an artificial censoring approach has been proposed to an isoform‐specific Poisson regression model for analyzing RNA‐seq data. Low expression values can be grouped (censored) into one probability category, and high expression values can also be grouped (censored) into another probability category. We have implemented the related Newton‐Raphson numeric computing procedure to achieve the maximum likelihood estimation for our censored‐Poisson regression model. The related mathematical simplifications have been derived for the consideration of stable and convenient numerical computing.

Results

The advantages of our artificial censoring approach have been demonstrated in both simulation studies and application analysis of experimental data.

Conclusions

Our proposed artificial censoring approach allows us to focus on the majority of data. As the extreme values (tails) of data are artificially censored, more efficient analysis results can be obtained, even from relatively simple Poisson regression models. Our proposed artificial censoring approach can certainly be considered for other well‐developed models or methods for RNA‐seq data analysis.
FTIR analysis and monitoring of used synthetic oils operated under similar driving conditions
Authors: Wolak Artur , Krasodomski Wojciech , Zając Grzegorz
Published: June 2020

The processes of degradation of engine oils operated in passenger cars of a uniform fleet of 25 vehicles were analyzed for oxidation content using infrared (IR) spectroscopy. As part of the experiment, the changes in engine oils occurring during actual operation (under conditions which can be described as “harsh”, i.e., short distance driving, frequent starting of the engine, and extended engine idling) have been observed. An evaluation of the Fourier transform infrared spectroscopy (FTIR) spectrum of an engine oil sample was presented. The infrared spectra of both fresh and used oils were recorded with the Thermo Nicolett IS5. The tests were conducted according to the Appendix A2 of ASTM 2412. For the used engine oil differentiation process, FTIR spectra were analyzed in the regions of 1,700–2,000 cm−1 and 3,600-3,700 cm−1. The FTIR spectrometry is demonstrated to be effective for the analysis and monitoring of processes of oxidation and shown to provide rapid and accurate information relating to the aging process of engine oils. The results may facilitate decision-making regarding the service life of engine oils. The achieved dependencies can make it possible to upgrade the sensor assembly consisting of an FTIR source.
Microbial Indicators of Fecal Pollution: Recent Progress and Challenges in Assessing Water Quality
Authors: Holcomb David A. , Stewart Jill R.
Published: June 2020

Purpose of Review

Fecal contamination of water is a major public health concern. This review summarizes recent developments and advancements in water quality indicators of fecal contamination.

Recent Findings

This review highlights a number of trends. First, fecal indicators continue to be a valuable tool to assess water quality and have expanded to include indicators able to detect sources of fecal contamination in water. Second, molecular methods, particularly PCR-based methods, have advanced considerably in their selected targets and rigor, but have added complexity that may prohibit adoption for routine monitoring activities at this time. Third, risk modeling is beginning to better connect indicators and human health risks, with the accuracy of assessments currently tied to the timing and conditions where risk is measured.

Research has advanced although challenges remain for the effective use of both traditional and alternative fecal indicators for risk characterization, source attribution and apportionment, and impact evaluation.
In Verteidigung der Rückhaltlosigkeit der menschlichen Geburt
Authors: Mitscherlich-Schönherr Olivia
Published: June 2020

In meinem Kommentar gehe ich von dem Verständnis der menschlichen Geburt in der Moderne aus, das Tatjana Tarkian mit vielen teilt: dem Verständnis, dass die menschliche Geburt in der Moderne ein autonom plan- und durchführbares „Projekt“ (Tarkian, Abschnitt 5) bilde. Im ersten Schritt meiner Überlegungen zeige ich, dass diese Vorstellung reduktionistisch ist: sie blendet sowohl die Widerfahrensaspekte als auch die dialogische Anlage der Geburt ab. In den weiteren Schritten meiner Überlegungen skizziere ich, dass Tarkians reduktionistisches Verständnis der menschlichen Geburt auf die Modulation ihrer Forschungsfrage und auf ihr normatives Leitprinzip durchschlägt – und dort eigene Abstraktionen hervorruft. Nur da Tarkian die Geburt als „Projekt“ der eigenen Reproduktion versteht, können sich ihr die Entscheidungen, zu denen pränatalmedizinische Tests befähigen, als „Auswahl“ zwischen „gesunden Kindern“ und „Kindern mit gesundheitlichen Beeinträchtigungen oder Normabweichungen“ (Tarkian, Abschnitt 3) darstellen. Und nur da sie die Geburt in Analogie zu anderen „Lebensprojekten“ versteht, kann sie ihr Leitprinzip der Freiheit im Gebären als reproduktive Handlungsfreiheit deuten – um zu diskutieren, ob die reproduktive Handlungsfreiheit beim Gebrauch pränatalmedizinischer Angebote an Grenzen stoße, da sie Anderen schade.