bluuebunny/crossref_metadata_2025 huggingface dataset:
P2X7R antagonists in chronic stress-based depression models: a review
Authors: von Muecke-Heim Iven-Alex , Ries Clemens , Urbina Lidia , Deussing Jan M.
Published: July 2021

Depression affects around 320 million people worldwide. Growing evidence proposes the immune system to be the core interface between psychosocial stress and the neurobiological and behavioural features of depression. Many studies have identified purinergic signalling via the P2X7 receptor (P2X7R) to be of great importance in depression genesis yet only a few have evaluated P2X7R antagonists in chronic stress-based depression models. This review summarizes their findings and analyses their methodology. The four available studies used three to nine weeks of unpredictable, chronic mild stress or unpredictable, chronic stress in male mice or rats. Stress paradigm composition varied moderately, with stimuli being primarily psychophysical rather than psychosocial. Behavioural testing was performed during or after the last week of stress application and resulted in depressive-like behaviours, immune changes (NLRP3 assembly, interleukin-1β level increase, microglia activation) and neuroplasticity impairment. During the second half of each stress paradigm, a P2X7R antagonist (Brilliant Blue G, A-438079, A-804598) was applied. Studies differed with regard to antagonist dosage and application timing. Nonetheless, all treatments attenuated the stress-induced neurobiological changes and depressive-like behaviours. The evidence at hand underpins the importance of P2X7R signalling in chronic stress and depression. However, improvements in study planning and reporting are necessary to minimize experimental bias and increase data purview. To achieve this, we propose adherence to the Research Domain Criteria and the STRANGE framework.
Presynaptic GABAB receptor–mediated network excitation in the medial prefrontal cortex of Tsc2+/- mice
Authors: Bassetti Davide , Luhmann Heiko J. , Kirischuk Sergei
Published: July 2021

The TSC1 and TSC2 tumor suppressor genes control the activity of mechanistic target of rapamycin (mTOR) pathway. Elevated activity of this pathway in Tsc2+/- mouse model leads to reduction of postsynaptic GABAB receptor–mediated inhibition and hyperexcitability in the medial prefrontal cortex (mPFC). In this study, we asked whether presynaptic GABAB receptors (GABABRs) can compensate this shift of hyperexcitability. Experiments were performed in brain slices from adolescent wild-type (WT) and Tsc2+/- mice. Miniature and spontaneous postsynaptic currents (m/sPSCs) were recorded from layer 2/3 pyramidal neurons in mPFC using patch-clamp technique using a Cs+-based intrapipette solution. Presynaptic GABABRs were activated by baclofen (10 µM) or blocked by CGP55845 (1 µM). Independent on genotype, GABABR modulators bidirectionally change miniature excitatory postsynaptic current (mEPSC) frequency by about 10%, indicating presynaptic GABABR-mediated effects on glutamatergic transmission are comparable in both genotypes. In contrast, frequencies of both mIPSCs and sIPCSs were suppressed by baclofen stronger in Tsc2+/- neurons than in WT ones, whereas CGP55845 significantly increased (m/s)IPSC frequencies only in WT cells. Effects of baclofen and CGP55845 on the amplitudes of evoked (e)IPSCs confirmed these observations. These data indicate (1) that GABAergic synapses are inhibited by ambient GABA in WT but not in Tsc2+/- slices, and (2) that baclofen shifts the E/I ratio, determined as the ratio of (m/s)EPSC frequency to (m/s)IPSC frequency, towards excitation only in Tsc2+/- cells. This excitatory presynaptic GABABR-mediated action has to be taken into account for a possible medication of mental disorders using baclofen.

Graphical abstract
Kennwerte und teststatistische Güte des Veterans RAND 12-Item Health Survey (VR-12) bei Patienten mit chronischem Schmerz
Authors: Hüppe M. , Schneider K. , Casser H.-R. , Knille A. , Kohlmann T. , Lindena G. , Nagel B. , Nelles J. , Pfingsten M. , Petzke F.
Published: July 2021

Der Veterans RAND 12-Item Health Survey (VR-12) wurde als Selbstbeurteilungsverfahren zur Erfassung gesundheitsbezogener Lebensqualität 2016 in den Deutschen Schmerzfragebogen (DSF) aufgenommen und ersetzt den bis dahin verwendeten lizenzpflichtigen SF-12. Beide Verfahren haben 12 Items und führen zu einer körperlichen und einer psychischen Summenskala. Auswertungen der deutschen Version mit größerer Stichprobe zu Kennwerten und zur teststatistischen Güte des VR-12 bei Patienten mit chronischem Schmerz fehlen bislang.

Daten zum VR-12 und weiterer Verfahren des DSF wurden von 11.644 Patienten aus 31 an KEDOQ-Schmerz beteiligten Zentren ausgewertet. Die Patienten hatten den DSF vor Beginn einer angestrebten schmerztherapeutischen Behandlung ausgefüllt. Die Bestimmung der Änderungssensitivität erfolgte für 565 Patienten, für die der VR-12 aus einem Verlaufsfragebogen des DSF mehrere Monate nach der Ersterhebung vorlag.

Die Reliabilität (Cronbachs Alpha) der körperlichen Summenskala war rtt = 0,78 und für die psychische Summenskala rtt = 0,84. Die psychische Summenskala wies deutliche Beziehungen zu den Depression-Angst-Stress-Skalen (DASS) auf (r = −0,51 bis r = −0,72), die körperliche Summenskala korrelierte höher mit Bereichen schmerzbedingter Beeinträchtigungen (r = −0,48 bis r = −0,52). Patienten mit höherer Schmerzchronifizierung, solche mit höherem Schmerz-Schweregrad und solche mit Hinweis auf hohe psychische Belastung beschrieben in beiden Summenskalen signifikant geringere gesundheitsbezogene Lebensqualität. Die Effektstärke (ES) der Veränderung im Sinne einer Verbesserung der gesundheitsbezogenen Lebensqualität war in der psychischen Summenskala ES = 0,33 und in der körperlichen Summenskala ES = 0,51.

Die Ergebnisse sind in Übereinstimmung zu Befunden zum SF-36 bzw. SF-12 bei anderen Patientenkollektiven mit chronischem Schmerz. Sie zeigen zusammengefasst, dass mit dem VR-12 ein angemessener Ersatz zum SF-12 im Deutschen Schmerzfragebogen integriert wurde.
Hausdorff’s forgotten proof that almost all numbers are normal
Authors: Weitz Edmund
Published: July 2021

In 1914, Felix Hausdorff published an elegant proof that almost all numbers are simply normal in base 2. We generalize this proof to show that almost all numbers are normal. The result is arguably the most elementary proof for this theorem so far and should be accessible to undergraduates in their first year.
Translation and modulation invariant Hilbert spaces
Authors: Toft Joachim , Gumber Anupam , Manna Ramesh , Ratnakumar P. K.
Published: July 2021

Let$$\mathcal H$$Hbe a Hilbert space of distributions on$$\mathbf{R}^{d}$$Rdwhich contains at least one non-zero element of the Feichtinger algebra$$S_0$$S0and is continuously embedded in$$\mathscr {D}'$$D′. If$$\mathcal H$$His translation and modulation invariant, also in the sense of its norm, then we prove that$$\mathcal H= L^2$$H=L2, with the same norm apart from a multiplicative constant.
Oxygenation Status of Malignant Tumors vs. Normal Tissues: Critical Evaluation and Updated Data Source Based on Direct Measurements with pO2 Microsensors
Authors: Vaupel Peter , Flood Ann Barry , Swartz Harold M.
Published: July 2021

Immature and chaotic vascular networks with critically increased intervascular distances are characteristic features of malignant tumors. Spatial and temporal heterogeneities of blood flow and associated availabilities of O2, together with limited diffusive O2 transport, and -in some patients- anemia, obligatorily lead to tumor hypoxia (= critically reduced O2 levels) on macro- and microscopic scales. This detrimental condition, recently classified as a key hallmark of malignant growth, acts (a) as a barrier in most antitumor treatments, and (b) leads to malignant progression based on hypoxia-induced changes of the genome, transcriptome, and proteome, and finally to poor patient survival. This knowledge is, to a great extent, based on the systematic detection of tumor hypoxia in the clinical setting since the late 1980s. Precise assessment of the tumor oxygenation status was made possible using minimally invasive polarographic pO2 microsensors in a series of research projects. To assess tumor hypoxia in the clinical setting, it is highly desirable to use technologies with (a) high spatial and temporal resolutions, (b) the capability to judge the severity of tumor hypoxia, (c) to allow mapping of pO2 of the whole tumor mass, and (d) to enable serial investigations in order to verify treatment-related changes in tumor hypoxia. Selection and treatment of cancer patients according to their individual tumor oxygenation/hypoxia status for intensified and/or personalized hypoxia-targeted treatment strategies should be the ultimate goal.
Multiscale Coupling of One-dimensional Vascular Models and Elastic Tissues
Authors: Heltai Luca , Caiazzo Alfonso , Müller Lucas O.
Published: July 2021

We present a computational multiscale model for the efficient simulation of vascularized tissues, composed of an elastic three-dimensional matrix and a vascular network. The effect of blood vessel pressure on the elastic tissue is surrogated via hyper-singular forcing terms in the elasticity equations, which depend on the fluid pressure. In turn, the blood flow in vessels is treated as a one-dimensional network. Intravascular pressure and velocity are simulated using a high-order finite volume scheme, while the elasticity equations for the tissue are solved using a finite element method. This work addresses the feasibility and the potential of the proposed coupled multiscale model. In particular, we assess whether the multiscale model is able to reproduce the tissue response at the effective scale (of the order of millimeters) while modeling the vasculature at the microscale. We validate the multiscale method against a full scale (three-dimensional) model, where the fluid/tissue interface is fully discretized and treated as a Neumann boundary for the elasticity equation. Next, we present simulation results obtained with the proposed approach in a realistic scenario, demonstrating that the method can robustly and efficiently handle the one-way coupling between complex fluid microstructures and the elastic matrix.
Three-Dimensional (3D) Textiles in Architecture and Fashion Design: a Brief Overview of the Opportunities and Limits in Current Practice
Authors: Giglio Andrea , Paoletti Ingrid , Conti Giovanni Maria
Published: July 2021

Three-dimensional (3D) textiles prove characteristics in structures and performance which can be as attractive as to be the main object of a high number of research and applications in specialist markets (from small medical devices to large engineering structure) where the performance demands are severe ([1] in J Eng Fibers Fabr.). Nevertheless, much of the research has come from academia and there are few relatively small companies that, even if have expertise, lack the resources to develop R&D programmes. This prevents to broaden their application and to consolidate their use in new markets ([2] in Advances in 3D Textiles, pp 1-18). The paper aims at exploring the potentialities and future implementations of 3D textiles in architecture and fashion design. Both are fields where the demand to balance requirements of environmental sustainability, low time-consuming production and high performance is emerging, in their own respective scale. A set of more than 10 real case studies are collected and analysed with the aim at underlining the potentialities and the limits of 3D textiles in practice. The overview suggests that a more integrated workflow among modelling and simulation tools and bigger effort from industry to enhance manufacturing options and increase the interest on new material systems, bring about new application such as indoor environmental quality (IEQ) or human body protection.
Urban Boundary Layers Over Dense and Tall Canopies
Authors: Makedonas Alexandros , Carpentieri Matteo , Placidi Marco
Published: July 2021

Wind-tunnel experiments were carried out on four urban morphologies: two tall canopies with uniform height and two super-tall canopies with a large variation in element heights (where the maximum element height is more than double the average canopy height, $$h_{max}=2.5h_{avg}$$

h

max

=
2.5

h

avg

). The average canopy height and packing density are fixed across the surfaces to $$h_{avg} = 80~\hbox {mm}$$

h

avg

=
80

mm

, and $$\lambda _{p} = 0.44$$

λ
p

=
0.44

, respectively. A combination of laser Doppler anemometry and direct-drag measurements are used to calculate and scale the mean velocity profiles with the boundary-layer depth $$\delta $$
δ
. In the uniform-height experiment, the high packing density results in a ‘skimming flow’ regime with very little flow penetration into the canopy. This leads to a surprisingly shallow roughness sublayer (depth $$\approx 1.15h_{avg}$$

≈
1.15

h

avg

), and a well-defined inertial sublayer above it. In the heterogeneous-height canopies, despite the same packing density and average height, the flow features are significantly different. The height heterogeneity enhances mixing, thus encouraging deep flow penetration into the canopy. A deeper roughness sublayer is found to exist extending up to just above the tallest element height (corresponding to $$z/h_{avg} = 2.85$$

z
/

h

avg

=
2.85

), which is found to be the dominant length scale controlling the flow behaviour. Results point toward the existence of a constant-stress layer for all surfaces considered herein despite the severity of the surface roughness ($$\delta /h_{avg} = 3 - 6.25$$

δ
/

h

avg

=
3
-
6.25

). This contrasts with the previous literature.
Concomitant Trajectories of Internalising, Externalising, and Peer Problems Across Childhood: a Person-centered Approach
Authors: Girard Lisa-Christine
Published: July 2021

This study investigated trajectories of concomitant internalising, externalising, and peer problems, and associated risk factors for group-membership, using a person-centered approach to better understand heterogeneity in subgroups identified. A cohort of 7,507 children in Ireland was followed from infancy to late childhood (50.3%, males; 84.9% Irish). The parent-version of the Strengths and Difficulties Questionnaire was used when children were 3, 5, 7 and 9 years of age. Information on antecedent risk factors was collected when children were 9 months. Group-based multi-trajectory modelling and multinomial logistic regression were used. Six subgroups of children with distinct profiles were identified, evidencing both homotypic and heterotypic comorbidity. No support of a ‘pure’ internalising, externalising or peer problems group was found in any identified trajectory group. Difficulties in one problem domain indicated the presence of difficulty in another problem domain for all children in elevated groups. Risk factors associated with group-membership were complex, with only three common factors across elevated groups: prenatal exposure to smoking, maternal education, and maternal stress. Specific risk factors for group-membership included low birth weight, sex, maternal age, maternal depression, family composition, social class, medical card status and quality of attachment. Despite some overlap in predictors, the combination of predictors specific to each group would suggest tailored programming. For children with the most acute problems, programming targets should include families with boys, born with low birth weight, exposed to smoking prenatally, with mothers who have lower levels of education, postnatal depression, increased stress and fewer financial resources.
Sequential learning to accelerate discovery of alkali-activated binders
Authors: Völker Christoph , Firdous Rafia , Stephan Dietmar , Kruschwitz Sabine
Published: July 2021

Alkali-activated binders (AAB) can provide a clean alternative to conventional cement in terms of CO2emissions. However, as yet there are no sufficiently accurate material models to effectively predict the AAB properties, thus making optimal mix design highly costly and reducing the attractiveness of such binders. This work adopts sequential learning (SL) in high-dimensional material spaces (consisting of composition and processing data) to find AABs that exhibit desired properties. The SL approach combines machine learning models and feedback from real experiments. For this purpose, 131 data points were collected from different publications. The data sources are described in detail, and the differences between the binders are discussed. The sought-after target property is the compressive strength of the binders after 28 days. The success is benchmarked in terms of the number of experiments required to find materials with the desired strength. The influence of some constraints was systematically analyzed, e.g., the possibility to parallelize the experiments, the influence of the chosen algorithm and the size of the training data set. The results show the advantage of SL, i.e., the amount of data required can potentially be reduced by at least one order of magnitude compared to traditional machine learning models, while at the same time exploiting highly complex information. This brings applications in laboratory practice within reach.
Structurally nanoengineered antimicrobial peptide polymers: design, synthesis and biomedical applications
Authors: Ramamurthy Ronisha , Mehta Chetan H. , Nayak Usha Y.
Published: July 2021

Antimicrobial resistance not only increases the contagiousness of infectious diseases but also a threat for the future as it is one of the health care concern around the globe. Conventional antibiotics are unsuccessful in combating chronic infections caused by multidrug-resistant (MDR) bacteria, therefore it is important to design and develop novel strategies to tackle this problems. Among various novel strategies, Structurally Nanoengineered Antimicrobial Peptide Polymers (SNAPPs) have been introduced in recent years to overcome this global health care issue and they are found to be more efficient in their performance. Many facile methods are adapted to synthesize complex SNAPPs with required dimensions and unique functionalities. Their unique characteristics and remarkable properties have been exploited for their immense applications in various fields including biomedicine, targeting therapies, gene delivery, bioimaging, and many more. This review article deals with its background, design, synthesis, mechanism of action, and wider applications in various fields of SNAPPs.

Graphic abstract
Stratigraphic analysis of intercalated graphite electrodes in aqueous inorganic acid solutions
Authors: De Rosa Stefania , Branchini Paolo , Spampinato Valentina , Franquet Alexis , Yivlialin Rossella , Duò Lamberto , Bussetti Gianlorenzo , Tortora Luca
Published: July 2021

A detailed stratigraphic investigation of the intercalation mechanism when graphite electrodes are immersed inside diluted perchloric (HClO4) and sulfuric (H2SO4) electrolytes is obtained by comparing results when graphite crystals are simply immersed in the same acid solutions. By combining time-of-flight secondary ion mass spectrometry (ToF-SIMS) and in-situ atomic force microscopy (AFM), we provide a picture of the chemical species involved in the intercalation reaction. The depth intensity profile of the ion signals along the electrode crystal clearly shows a more complex mechanism for the intercalation process, where the local morphology of the basal plane plays a crucial role. Solvated anions are mostly located within the first tens of nanometers of graphite, but electrolytes also diffuse inside the buried layers for hundreds of nanometers, the latter process is also aided by the presence of mesoscopic crystal defects. Residual material from the electrolyte solution was found localized in well-defined circular spots, which represent preferential interaction areas. Interestingly, blister-like micro-structures similar to those observed on the highly oriented pyrolytic graphite (HOPG) surface were found in the buried layers, confirming the equivalence of the chemical condition on the graphite surface and in the underneath layers.
Applying mechanical philosophy to web science: The case of social machines
Authors: Smart Paul R. , O’Hara Kieron , Hall Wendy
Published: July 2021

Social machines are a prominent focus of attention for those who work in the field of Web and Internet science. Although a number of online systems have been described as social machines (examples include the likes of Facebook, Twitter, Wikipedia, Reddit, and Galaxy Zoo), there is, as yet, little consensus as to the precise meaning of the term “social machine.” This presents a problem for the scientific study of social machines, especially when it comes to the provision of a theoretical framework that directs, informs, and explicates the scientific and engineering activities of the social machine community. The present paper outlines an approach to understanding social machines that draws on recent work in the philosophy of science, especially work in so-called mechanical philosophy. This is what might be called a mechanistic view of social machines. According to this view, social machines are systems whose phenomena (i.e., events, states, and processes) are explained via an appeal to (online) socio-technical mechanisms. We show how this account is able to accommodate a number of existing attempts to define the social machine concept, thereby yielding an important opportunity for theoretical integration.
Impact of tailored water chemistry aqueous ions on foam stability enhancement
Authors: AlYousef Zuhair , Ayirala Subhash , Almubarak Majed , Cha Dongkyu
Published: July 2021

Generating strong and stable foam is necessary to achieve in-depth conformance control in the reservoir. Besides other parameters, the chemistry of injection water can significantly impact foam generation and stabilization. The tailored water chemistry was found to have good potential to improve foam stability. The objective of this study is to extensively evaluate the effect of different aqueous ions in the selected tailored water chemistry formulations on foam stabilization. Bulk and dynamic foam experiments were used to evaluate the impact of different tailored water chemistry aqueous ions on foam generation and stabilization. For bulk foam tests, the stability of foams generated using three surfactants and different aqueous ions was analyzed using bottle tests. For dynamic foam experiments, the tests were conducted using a microfluidic device. The results clearly demonstrated that the ionic content of aqueous solutions can significantly affect foam stabilization. The results revealed that the foam stabilization in bulk is different than that in porous media. Depending on the surfactant type, the divalent ions were found to have stronger influence on foam stabilization when compared to monovalent ions. The bulk foam results pointed out that the aqueous solutions containing calcium chloride salt (CaCl2) showed longer foam life with the anionic surfactant and very weak foam with the nonionic surfactant. The solutions with magnesium chloride (MgCl2) and CaCl2 salts displayed higher impact on foam stability in comparison with sodium chloride (NaCl) with the amphoteric alkyl amine surfactant. Less stable foams were generated with aqueous solutions comprising of both magnesium and calcium ions. In the microfluidic model, the solutions containing MgCl2 showed higher resistance to gas flow and subsequently higher mobility reduction factor for the injection gas when compared to those produced using NaCl and CaCl2 salts. This experimental study focusing about the role of different aqueous ions in the injection water on foam could help in better understanding the foam stabilization process. The new knowledge gained can also enable the selection and optimization of the right injection water chemistry and suitable chemicals for foam field applications.
Outcomes of Macrosurgical Versus Microsurgical Vasovasostomy in Vasectomized Men: a Systematic Review and Meta-analysis
Authors: Duijn M. , van der Zee J. A. , Bachour Y.
Published: July 2021

In order to restore fertility by vasectomy reversal, vasovasostomy (VV) is one of the most chosen options. During this procedure, the vas deferens is anastomosed either by a macro- or microscopical technique. Up to date, it is unknown which of these techniques shows best overall post-procedure patency and pregnancy rates. The purpose of this systematic review and meta-analysis is to reach a consensus on which technique is best for vasovasostomy and thereby better counsel patients and practitioners. A systematic review and meta-analysis on macroscopic and microscopic VV for vasectomy reversal was performed. PubMed, The Cochrane Library, Embase, and Web of Science were systematically searched from inception until 2019. Studies and associated data were evaluated by two reviewers. Primary, data on post-operative patency and pregnancy rates, interval to reversal, and post-operative complications were extracted. Proportions (95% CI) and heterogeneity scores (I2) were calculated, using a random effects model. A total of 8305 patients were included by 25 studies. Descriptive analysis showed higher post-operative patency (80.5% vs 91.4%) and pregnancy rates (47.7% vs 73.3%) after microscopic vasovasostomy. Meta-analysis produced post-operative patency proportions of 0.80 (95% CI, 0.76–0.84) and 0.88 (95% CI, 0.83–0.92) after macro- and microscopic VV respectively. Proportions of post-operative pregnancy were 0.43 (95% CI, 0.35–0.50) after macroscopic VV and 0.47 (95% CI, 0.31–0.62) after microsurgical VV. Microscopic VV is associated with higher post-operative patency and pregnancy rates compared to macroscopic vasovasostomy. However, further research is needed because of shortage in high methodological quality and variety.
A New Paradigm for Safety Data Signal Detection and Evaluation Using Open-Source Software Created by an Interdisciplinary Working Group
Authors: Buchanan James , Li Mengchun , Ni Xiao , Wildfire Jeremy
Published: July 2021

Techniques to evaluate large amounts of safety data continue to evolve based on a greater understanding of how the brain processes visual information and the advancement of programing tools. The Interactive Safety Graphics Task Force of the American Statistical Association Biopharmaceutical Safety Working Group has assembled a multidisciplinary team of experts in a variety of domains to develop the next generation of open-source visual analytical tools for safety data based on these advances. The multidisciplinary approach resulted in the rapid development of the first tool, a novel interactive version of the familiar Evaluation of Drug-Induced Serious Hepatotoxicity (eDISH) graphic along with a unique clinical workflow to guide the reviewer through the data analysis. This now serves as the model for the team to expand the open-source platform into a suite of other interactive safety analysis tools.
The Concealment Controversy
Authors: Wessels Janna
Published: July 2021

The idea that a claim for international protection can be rejected on the basis that the claimant behave 'discreetly' in their country of origin has remained resilient in asylum claims based on sexual orientation, but also other grounds of claim. This is significant because requiring an asylum-seeker to forgo the reason for which they are persecuted questions the very rationale of refugee protection. This book represents the first principled examination of concealment in refugee law. Janna Wessels connects the different strands of the long-standing debate in both common and civil law jurisdictions and scholarship concerning the question of whether and under which circumstances a claimant must conceal to avoid persecution. In so doing, Wessels uncovers a fundamental tension at the core of the refugee concept. By using sexuality as a lens, this study breaks new ground regarding sexual orientation claims and wider issues surrounding the refugee definition.
A NOTE ON GROUP RINGS WITH TRIVIAL UNITS
Authors: CHIN A. Y. M.
Published: July 2021

Let R be a ring with identity of characteristic two and G a nontrivial torsion group. We show that if the units in the group ring
$RG$
are all trivial, then G must be cyclic of order two or three. We also consider the case where R is a commutative ring with identity of odd prime characteristic and G is a nontrivial locally finite group. We show that in this case, if the units in
$RG$
are all trivial, then G must be cyclic of order two. These results improve on a result of Herman et al. [‘Trivial units for group rings with G-adapted coefficient rings’, Canad. Math. Bull.48(1) (2005), 80–89].
U-shaped association between dietary calcium density intake during adolescence and hypertension in adulthood: a 20-year longitudinal nationwide study in China
Authors: Sun Xiaomin , Shi Zumin , Li Yixuan , Xin Bao , Li Xi , Wang Youfa
Published: July 2021

We assessed longitudinal association between calcium intake during adolescence and hypertension in adulthood. Longitudinal study data of 1611 participants from the China Health and Nutrition Survey during 1991–2011 were used. On average they were followed for 11·4 years. Dietary calcium intake during adolescence was assessed based on three 24-hour dietary recalls collected in each visit/survey between 1991 and 2009 (seven waves). The intake was recoded into quartiles. Cumulative mean±SD calcium intake was 199·9±144·8 mg/1000 kcal/day during adolescence. In total 102 participants had hypertension in adulthood (97 men and 5 women). There was a clear U-shaped association between adolescence calcium intake quartiles and adulthood hypertension: across the quartiles, hypertension prevalence was 6·7%, 4·0%, 5·2% and 9·5%, respectively. After adjustment for potential confounders including weight status and dietary pattern, odds ratios (OR, 95% CI) for hypertension were 2·32 (95% CI 1·07–5·00) for lowest quartile, 1·00 (reference), 1·34 (95% CI 0·61–2·97), and 3·10 (95% CI 1·49–6·46) across the quartiles. Lower or higher calcium intake during adolescence was associated with hypertension in adulthood independent of weight status and dietary pattern.
Using major depression polygenic risk scores to explore the depressive symptom continuum
Authors: Jermy Bradley S. , Hagenaars Saskia P. , Glanville Kylie P. , Coleman Jonathan R. I. , Howard David M. , Breen Gerome , Vassos Evangelos , Lewis Cathryn M.
Published: July 2021

Background

Major depression (MD) is often characterised as a categorical disorder; however, observational studies comparing sub-threshold and clinical depression suggest MD is continuous. Many of these studies do not explore the full continuum and are yet to consider genetics as a risk factor. This study sought to understand if polygenic risk for MD could provide insight into the continuous nature of depression.

Methods

Factor analysis on symptom-level data from the UK Biobank (N= 148 957) was used to derive continuous depression phenotypes which were tested for association with polygenic risk scores (PRS) for a categorical definition of MD (N= 119 692).

Results

Confirmatory factor analysis showed a five-factor hierarchical model, incorporating 15 of the original 18 items taken from the PHQ-9, GAD-7 and subjective well-being questionnaires, produced good fit to the observed covariance matrix (CFI = 0.992, TLI = 0.99, RMSEA = 0.038, SRMR = 0.031). MD PRS associated with each factor score (standardisedβrange: 0.057–0.064) and the association remained when the sample was stratified into case- and control-only subsets. The case-only subset had an increased association compared to controls for all factors, shown via a significant interaction between lifetime MD diagnosis and MD PRS (pvalue range: 2.23 × 10−3–3.94 × 10−7).

Conclusions

An association between MD PRS and a continuous phenotype of depressive symptoms in case- and control-only subsets provides support against a purely categorical phenotype; indicating further insights into MD can be obtained when this within-group variation is considered. The stronger association within cases suggests this variation may be of particular importance.
Perfect matchings, rank of connection tensors and graph homomorphisms
Authors: Cai Jin-Yi , Govorov Artem
Published: July 2021

We develop a theory of graph algebras over general fields. This is modelled after the theory developed by Freedman et al. (2007, J. Amer. Math. Soc.20 37–51) for connection matrices, in the study of graph homomorphism functions over real edge weight and positive vertex weight. We introduce connection tensors for graph properties. This notion naturally generalizes the concept of connection matrices. It is shown that counting perfect matchings, and a host of other graph properties naturally defined as Holant problems (edge models), cannot be expressed by graph homomorphism functions with both complex vertex and edge weights (or even from more general fields). Our necessary and sufficient condition in terms of connection tensors is a simple exponential rank bound. It shows that positive semidefiniteness is not needed in the more general setting.
Kawasaki disease shock syndrome in the COVID-19 pandemic
Authors: Gámez-González Luisa B. , Ramírez-López Moises J. , Colmenero-Rascón Marcela , Yamazaki-Nakashimada Marco A.
Published: July 2021

Multisystem inflammatory syndrome in children is a new entity in association with SARS-CoV2. Clinical features of Kawasaki disease were noted from the first reported cases of MIS-C. Before the COVID-19 pandemic, Kawasaki disease shock syndrome was considered to be a distinct and unique form of KD. We present a representative case that prove the current difficulty in clearly distinguishing MIS-C from pre-COVID-19-KDSS and emphasie the overlap of the diagnostic criteria.
Multiple emotions, multiple selves: compassion focused therapy chairwork
Authors: Bell Tobyn , Montague Jane , Elander James , Gilbert Paul
Published: July 2021

Compassion focused therapy (CFT) is rooted in an evolutionary view of the human mind as formed of a multitude of contrasting, and often conflicting, motivations, emotions and competencies. A core aim of the therapy is to help clients understand the nature of their mind in a way that is de-pathologizing and de-shaming. The approach is also focused on the cultivation of compassion to work with these difficult aspects of mind. CFT includes the ‘multiple-selves’ intervention which involves the differentiation of threat-based emotion and an exploration of their conflict. Compassion is then applied to the client’s affective world to aid regulation and integration. This paper focuses on clients’ experiences of a chairwork version of multiple-selves, wherein clients personify their emotions in separate chairs. Nine participants with depression were interviewed directly following the intervention and the resulting data were analysed using interpretative phenomenological analysis. Three interconnecting themes were identified: appreciating emotional complexity; the role of chairwork process; and compassionate integration. The results highlight the importance of emotional differentiation in understanding internal multiplicity and conflict in depression, and the role of compassion in creating a sense of personal coherence. The embodied and enactive nature of chairwork was found to be of benefit in identifying and separating emotion, and in developing new forms of self-relating. The paper discusses the clinical implications of such findings for the treatment of depression.

Key learning aims

As a result of reading this paper, readers should:

(1)

Learn about the ‘multiple-selves’ framework for working with threat emotions.

(2)

Appreciate the complexity of emotions in depression.

(3)

Understand how chairwork processes can be used to access, differentiate and address emotional material.

(4)

Develop insight into how compassion can be used to regulate emotions and integrate aversive experiences.
On prisoners, family life and collective punishment: The Namnam case
Authors: Ronen Yaël
Published: July 2021

This article examines the 2019 decision by the Supreme Court of Israel (the Court) in the Namnam case, upholding a ban on family visits to Gaza prisoners incarcerated in Israel and affiliated with Hamas.1 This ban was adopted as part of Israel's attempt to pressure Hamas into an exchange of Palestinian detainees and prisoners against missing Israeli civilians and the bodies of Israeli soldiers, apparently being held by Hamas in Gaza. The Court examined the measure primarily in light of Israeli administrative law, and held that it had no grounds to intervene. It held that an analysis under international law would have yielded the same result.

This article examines the decision of the Court in light of the applicable international law. It considers the Court's decision in terms of the permissible restrictions on the right to family life and draws on the Court's reasoning for an in-depth analysis of various unarticulated aspects of the prohibition on collective punishment. The article concludes that an international human rights law analysis might have led to a different outcome, and that had the Court applied the prohibition on collective punishment properly, it would have had to declare the measure unlawful. The article then places the decision in the broader context of the Court's engagement with international law in disputes relating to Palestinians residing in the West Bank and Gaza.
Low Frequency ULF Waves in the Earth's Inner Magnetosphere: Statistics During Coronal Mass Ejections and Seeding of EMIC Waves
Authors: Gamayunov Konstantin V. , Engebretson Mark J.
Published: July 2021

Here we perform a statistical analysis of low frequency ultra‐low‐frequency (ULF) waves ( mHz ‐ Hz) in the Earth's inner magnetosphere excluding electromagnetic ion cyclotron waves concurrently observed. We use the magnetic field data from the two Van Allen Probes during their first magnetic local time (MLT) revolution that cover the periods of coronal mass ejections. The major results of our analysis are as follows. (a) Spectra of both the transverse and compressional ULF waves are well approximated by the power‐laws in the mHz ‐ Hz frequency range. (b) There are two sources of the low frequency ULF waves: an internal magnetospheric source and an external source outside of the magnetosphere. (c) The average transverse power in the 6–24 h MLT sector dominates that in the 0–6 h sector, whereas the compressional power in the 12–24 h sector dominates that in the 0–12 h sector. (d) The average powers of transverse and compressional ULF waves in the plasmasphere dominate the average powers in the high L shell region of , and there is a deep power minimum in the intermediary region of . (e) The compressional ULF wave power has a maximum in the near equatorial region, whereas the transverse power has a minimum there. (f) A wave energy cascade from low frequency ULF waves into the higher frequency range of EMIC waves ( Hz) supplies the nonthermal seed fluctuations from which EMIC waves can then grow due to instabilities of the energetic magnetospheric ions.
Downscaling Snow Deposition Using Historic Snow Depth Patterns: Diagnosing Limitations From Snowfall Biases, Winter Snow Losses, and Interannual Snow Pattern Repeatability
Authors: Pflug J. M. , Hughes M. , Lundquist J. D.
Published: July 2021

Repeatable snow depth patterns have been identified in many regions between years with similar meteorological characteristics. This suggests that snow patterns from previous years could adjust snow deposition in space as a substitution for unmodeled snow processes. Here, we tested a pattern‐based snow deposition downscaling routine which assumes (a) a spatially consistent relationship between snow deposition and snow depth, (b) interannually repeatable snow patterns, and (c) unbiased mean snowfall. We investigated these assumptions, and future avenues for improvement, in water‐year 2014 over the California Tuolumne River Watershed. 6 km snowfall from an atmospheric model was downscaled to 25 m resolution using snow depth patterns from seven different years, and was compared to a more common terrain‐based downscaling method. Snow depth patterns were influenced not only by snow accumulation, but also snowmelt, snow sublimation, and snow density, resulting in pattern‐based snow deposition downscaling that was too spatially heterogeneous. However, snow depth simulated using terrain‐based downscaling was too spatially homogeneous, and less spatially correlated with observations (r = 0.27), than simulations with pattern‐based downscaling using snow depth patterns from the simulation season (r = 0.76), or from a different year (r = 0.52). Overall, modeled snow depth errors at peak‐snowpack timing were driven more by atmospheric model snowfall biases than different downscaling methods. In order of most‐ to least‐importance, future research should focus on bias‐correcting coarse‐scale snowfall estimates, correcting snow deposition patterns for winter snow losses and snow density spatial variability, and identifying the historic periods of most‐similar snow accumulation.
A Multi‐Inventory Ensemble Analysis of the Effects of Atmospheric Rivers on Precipitation and Streamflow in the Namgang‐Dam Basin in Korea
Authors: Ryu Young , Moon Hyejin , Kim Jinwon , Kim Tae‐Jun , Boo Kyung‐On , Guan Bin , Kamae Yoichi , Mei Wei , Park Chanil , Son Seok‐Woo , Byun Young‐Hwa
Published: July 2021

Atmospheric rivers (ARs) are an important concern in regional water management; however, little is known about the AR impacts on hydrology in East Asia (EA). This study analyzes the characteristics of storms, precipitation (P), streamflow (Q), and runoff coefficient (R) in the Namgang‐dam basin in Korea related to ARs for 2000–2013, as well as the sensitivity of the analysis results to AR detection methods, using observed P, Q, and three different AR inventories. The basin experiences 37.3 storms annually, of which 54% are AR storms that provide over 60% of the annual P and Q. The AR (non‐AR) storms are dominant in storm frequency and the storm‐total P and Q for January–July (August–December) with peaks in July (August). The monthly AR frequency varies closely with the seasonal variations in the EA monsoon and the North Pacific storm track which modulate the number of extratropical cyclones. The AR storms produce most of the extreme events; they also generate larger storm‐mean P and Q than the non‐AR storms for all months. The seasonal variations in R are related to the total (AR‐ and non‐AR storms combined) P through the seasonal soil water variations, making the AR effects on R unclear. Considering 95% confidence intervals, the AR storms are distinguished well from the non‐AR storms in storm frequency and the storm‐total and storm‐mean P and Q. The sensitivity to AR inventories is not critical in quantifying the AR‐storm characteristics and their impacts on hydrologic variables except for R.
Cancer cells escape p53’s tumor suppression through ablation of ZDHHC1-mediated p53 palmitoylation
Authors: Tang Jun , Peng Weiyan , Feng Yixiao , Le Xin , Wang Kang , Xiang Qin , Li Lili , Wang Yan , Xu Can , Mu Junhao , Xu Ke , Ji Ping , Tao Qian , Huang Ailong , Deng Chu-Xia , Lin Yong , Xiang Tingxiu
Published: July 2021

The inactivation of tumor-suppressor genes contributes heavily to oncogenesis. The mutation of TP53 has been well-studied and recognized as a major factor in the development of tumors. Yet other means of p53 inactivation has not been well-elucidated. We previously identified a hypermethylated gene ZDHHC1 that suppresses tumor growth when the expression was restored, but the specific mechanism was yet to be found. The protein product of ZDHHC1 is an S-palmitoyltransferase and we have identified p53 as a substrate for ZDHHC1-mediated palmitoylation, specifically at the C135, C176, and C275 residues. The novel form of post-translational modification of p53 is required for the nuclear translocation of the tumor suppressor. p53 recruited DNMT3A to ZDHHC1 promoter and is responsible for the hypermethylation of ZDHHC1. The epigenetic feedback loop formed by ZDHHC1 and p53 sheds light on the inactivation of p53 without the presence of genetic mutations.
Adversity in early life and pregnancy are immunologically distinct from total life adversity: macrophage-associated phenotypes in women exposed to interpersonal violence
Authors: Aschbacher Kirstin , Hagan Melissa , Steine Iris M. , Rivera Luisa , Cole Steve , Baccarella Alyssa , Epel Elissa S. , Lieberman Alicia , Bush Nicole R.
Published: July 2021

Early childhood and pregnancy are two sensitive periods of heightened immune plasticity, when exposure to adversity may disproportionately increase health risks. However, we need deeper phenotyping to disentangle the impact of adversity during sensitive periods from that across the total lifespan. This study examined whether retrospective reports of adversity during childhood or pregnancy were associated with inflammatory imbalance, in an ethnically diverse cohort of 53 low-income women seeking family-based trauma treatment following exposure to interpersonal violence. Structured interviews assessed early life adversity (trauma exposure ≤ age 5), pregnancy adversity, and total lifetime adversity. Blood serum was assayed for pro-inflammatory (TNF-a, IL-1ß, IL-6, and CRP) and anti-inflammatory (IL-1RA, IL-4, and IL-10) cytokines. CD14+ monocytes were isolated in a subsample (n = 42) and gene expression assayed by RNA sequencing (Illumina HiSeq 4000; TruSeq cDNA library). The primary outcome was a macrophage-associated M1/M2 gene expression phenotype. To evaluate sensitivity and specificity, we contrasted M1/M2 gene expression with a second, clinically-validated macrophage-associated immunosuppressive phenotype (endotoxin tolerance) and with pro-inflammatory and anti-inflammatory cytokine levels. Adjusting for demographics, socioeconomic status, and psychopathology, higher adversity in early life (ß = .337, p = 0.029) and pregnancy (ß = .332, p = 0.032) were each associated with higher M1/M2 gene expression, whereas higher lifetime adversity (ß = −.341, p = 0.031) was associated with lower immunosuppressive gene expression. Adversity during sensitive periods was uniquely associated with M1/M2 imbalance, among low-income women with interpersonal violence exposure. Given that M1/M2 imbalance is found in sepsis, severe COVID-19 and myriad chronic diseases, these findings implicate novel immune mechanisms underlying the impact of adversity on health.
Impact of COVID-19 lockdown on mental health in Germany: longitudinal observation of different mental health trajectories and protective factors
Authors: Ahrens K. F. , Neumann R. J. , Kollmann B. , Brokelmann J. , von Werthern N. M. , Malyshau A. , Weichert D. , Lutz B. , Fiebach C. J. , Wessa M. , Kalisch R. , Plichta M. M. , Lieb K. , Tüscher O. , Reif A.
Published: July 2021

The COVID-19 pandemic and resulting measures can be regarded as a global stressor. Cross-sectional studies showed rather negative impacts on people’s mental health, while longitudinal studies considering pre-lockdown data are still scarce. The present study investigated the impact of COVID-19 related lockdown measures in a longitudinal German sample, assessed since 2017. During lockdown, 523 participants completed additional weekly online questionnaires on e.g., mental health, COVID-19-related and general stressor exposure. Predictors for and distinct trajectories of mental health outcomes were determined, using multilevel models and latent growth mixture models, respectively. Positive pandemic appraisal, social support, and adaptive cognitive emotion regulation were positively, whereas perceived stress, daily hassles, and feeling lonely negatively related to mental health outcomes in the entire sample. Three subgroups (“recovered,” 9.0%; “resilient,” 82.6%; “delayed dysfunction,” 8.4%) with different mental health responses to initial lockdown measures were identified. Subgroups differed in perceived stress and COVID-19-specific positive appraisal. Although most participants remained mentally healthy, as observed in the resilient group, we also observed inter-individual differences. Participants’ psychological state deteriorated over time in the delayed dysfunction group, putting them at risk for mental disorder development. Consequently, health services should especially identify and allocate resources to vulnerable individuals.