bluuebunny/crossref_metadata_2025 huggingface dataset:
Healthy nutrition in Germany: a survey analysis of social causes, obesity and socioeconomic status
Authors: Mader Sebastian , Rubach Malte , Schaecke Wolfram , Röger Christine , Feldhoffer Ina , Thalmeier Eva-Magdalena
Published: April 2020

Objective:

The obesity pandemic is an increasing burden for society. Information on key drivers of the nutrition cycle of (a) social causation, (b) biological causation and (c) health selection is vital for effective policies targeted at the reduction of obesity prevalence. However, empirical causal knowledge on (a) the social predictors of diet quality, (b) its impact on corpulence and (c) the socioeconomic consequences of obesity is sparse. We overcome the limitations of previous research and acquire comprehensive causal insight into this cycle.

Design:

Therefore, we analyse two German socio-epidemiological panel surveys exploiting their longitudinal panel structure utilising hybrid panel regression models.

Setting:

General population of Germany.

Participants:

German Health Interview and Examination Survey for Children and Adolescents (KiGGS,n17 640; age 0–24 years) and the German National Nutrition Monitoring (NEMONIT,n2610; age 15–82 years).

Results:

The results indicate that (a) interestingly only sex, education and age explain healthy diets; (b) increases in a newly developed Optimised Healthy Eating Index (O-HEI-NVSII) and in nuts intake reduce BMI, while growing overall energy intake, lemonade, beer and meat (products) intake drive corpulence; (c) in turn, developing obesity decreases socioeconomic status.

Conclusions:

These results suggest that policies targeted at the reduction of obesity prevalence may be well advised to focus on boys and men, people with low education, the promotion of a healthy diet and nuts intake, and the limitation of lemonade, beer and meat (products) intake. Therefore, future research may focus on the replication of our findings utilising longer panels and experimental approaches.
The influence of current food and nutrition trends on dietitians’ perceptions of the healthiness of packaged food
Authors: Thurecht Rachael L , Pelly Fiona E , Cooper Sheri L
Published: April 2020

Objective:

To investigate the influence of current food and nutrition trends on dietitians’ perceptions of the healthiness of packaged foods.

Design:

This observational study used a cross-sectional survey. Participants rated (strongly disagree to strongly agree) the extent to which a range of factors, independent of the energy, nutrient and ingredient content, influenced their perceptions of the healthiness of packaged foods. Two open-ended questions allowed for participants to list additional items they considered important.

Setting:

Online survey.

Participants:

Australian dietitians (n 117).

Results:

The greatest consensus was a positive influence of the fit within the core food groups and presence of seasonal ingredients, and a negative influence of an increasing number of additives. Mixed opinions were obtained for GM ingredients, locally sourced ingredients, labelling of animal welfare and organic certification. Nutritional indicators received a split where almost half of participants disagreed/strongly disagreed that they positively influenced their perception of healthiness. Content analysis of open-ended responses (n 53, 45 %) revealed four broad categories as important in considering healthiness: ‘a whole food approach’, ‘marketing and labelling’, ‘product information’ and ‘context of diet’. A small number of responses (count of 6, 5 %) reported that packaging, advertising and features such as celebrity endorsement were a negative influence.

Conclusions:

Dietitians have a broad concept of the healthiness of packaged foods, which incorporates elements of food safety, wholeness of the ingredients and marketing. Providing unified messages to the consumer can help to build the public perception of dietitians as experts in nutrition advice and counselling.
Crio-fixation of Pachytene Cells
Authors: Ortiz-Hernandez R. , Vázquez-Nin G. H. , Echeverría-Martínez O. , Höög C. , Hernández-Hernández A.
Published: April 2020

Genetic variability in organisms with sexual reproduction is produced by a complex mechanism of cell division of the germ line cells known as meiosis. During meiosis, homologous chromosomes pair and exchange genetic material (meiotic recombination), process that is essential to complete the meiotic division and to produce variability. Homologous chromosome pairing is mediated by the synaptonemal complex (SC). The SC is a proteinaceous structure composed of two lateral elements (LEs) and a central region (CR). Any defect in SC structure impairs meiotic recombination leading to blockage of the cell division process and infertility1. The SC has been observed since the introduction of the electron microscope (EM) in the biological field and it has been reported to be present in almost all the organisms with sexual reproduction, conserving a very similar structure and organisation along the different species2,3. The classic approach to study the SC structure is to chemically fixate the sexual tissues (gonads), dehydrate and embedded them in plastic resins that provide a support for sample sectioning and observation under the EM. However, chemical fixation followed by dehydration is well known to produce artefacts in the structure of many biological samples. Recently, we have combined fluorescence activated cell sorting of cells with SCs with high-pressure freezing and freeze- substitution and have found that the structure of the CR looks different from that observed in chemically fixated samples. These data have prompted us to analyse the organization of the CR components under cryo-processing.
Developing short-season cotton genotypes with high harvest index might be an advantageous option under late duration plantings
Authors: Iqbal Muhammad , Khan Mueen Alam , Chattha Waqas Shafqat
Published: April 2020

Short duration cotton (Gossypium hirsutum L.) cultivar may be more profitable for the growers, as it will have shortened critical growth window for drought, heat and insect pests. Therefore, in the present research work, two cotton advance lines IUB-71 and IUB-73 along with an approved cotton cultivar IUB-13 were tested under four different sowing dates i.e. S1 (25th April), S2 (10th May), S3 (25th May) and S4 (10th June) in 2017 and 2018 under field condition. Field layout was RCBD factorial with four sowing dates as one factor and three cotton genotypes as another factor with three replications. Data were recorded for plant height, total number of nodes, bolls per plant, seed cotton yield (SCY), above ground fresh biomass (AGFB) and harvest index (HI). An overall decreasing trend with increasing sowing dates was observed in all the traits except HI that relatively increased in all the three genotypes. Within each sowing date, a higher value for each trait was observed for genotype IUB-73 except for AGFB might be due to higher reproductive allocation. It is concluded that IUB-73 due to superior SCY and HI specifically under late planting is best fit for short cotton seasons with reduced critical window for cotton management.
Integration of RF rectenna with thin film solar cell to power wearable electronics
Authors: Naresh B. , Singh Vinod Kumar , Sharma V. K.
Published: April 2020

This paper reports an integration of dual band microstrip antenna with thin film amorphous silicon solar cell which creates a wearable system to harvest microwave energy. The multiple layers in the encapsulation of the thin film solar cell are used as a substrate for microstrip antenna. The rectifier and matching circuit are designed on cotton jeans material and the whole system is mechanically supported by the foam of 5 mm thick. The performance of the antenna is studied for the mechanical bending condition. The device has maintained good power conversion efficiency. The efficiency of the voltage doubler is tested by varying radio frequency power levels from −30 to10 dBm. The voltage doubler conversion efficiency at 1.85 and 2.45 GHz are 58 and 43%, respectively, for a load of 7.5 kΩ for an input power level of −5 dBm.
Characterization of electrolyte content in urine samples through a differential microfluidic sensor based on dumbbell-shaped defected ground structures
Authors: Muñoz-Enano J. , Vélez P. , Gil M. , Jose-Cunilleras E. , Bassols A. , Martín F.
Published: April 2020

In this paper, a differential microfluidic sensor and comparator based on a pair of microstrip lines loaded with dumbbell-shaped defected ground structure resonators is applied to the characterization of electrolyte concentration in samples of horse urine. Since variations in the total electrolyte content in urine may be indicative of certain pathologies, the interest is to use the device as a comparator, in order to determine changes in the electrolyte concentration as compared to a reference level. To validate the approach, we have made differential measurements of a set of urine samples with different electrolyte concentrations (which have been previously obtained by means of electrochemical methods). The obtained results correlate with the nominal electrolyte concentrations of the samples, thereby pointing out the potential of the approach as a low-cost pre-screening method (or complementary diagnosis system) to detect potential pathologies or diseases in horses and other animals.
Repercussions of maternal exposure to high-fat diet on offspring feeding behavior and body composition: a systematic review
Authors: Chaves Wenicios Ferreira , Pinheiro Isabeli Lins , da Silva Jacqueline Maria , Manhães-de-Castro Raul , da Silva Aragão Raquel
Published: April 2020

Maternal nutrition is an environmental determinant for offspring growth and development, especially in critical periods. Nutritional imbalances during these phases can promote dysregulations in food intake and feeding preference in offspring, affecting body composition. The aim of this review is to summarize and discuss the effects of maternal high-fat diet (HFD) on offspring feeding behavior and body composition. A search was performed in the PUBMED, SCOPUS, Web of Science, and LILACS databases. Inclusion criteria were studies in rodents whose mothers were submitted to HFD that assessed outcomes of food or caloric intake on offspring and food preference associated or not with body weight or body composition analysis. At the end of the search, 17 articles with the proposed characteristics were included. In these studies, 15 articles manipulated diet during pregnancy and lactation, 1 during pregnancy only, and 1 during lactation only. Maternal exposure to a HFD leads to increased food intake, increased preference for HFDs, and earlier food independence in offspring. The offspring from HFD mothers present low birthweight but become heavier into adulthood. In addition, these animals also exhibited greater fat deposition on white adipose tissue pads. In conclusion, maternal exposure to HFD may compromise parameters in feeding behavior and body composition of offspring, impairing the health from conception until adulthood.
Wandering Money: Valuating and Mediating Post-War Remittances in Vietnam
Authors: Small Ivan V.
Published: April 2020

Remittances from the Vietnamese diaspora have played an important role in Vietnam's post-Cold War economic development, providing important inputs to a range of household spending areas, from education to health care. In the case of Vietnam, however, remittances are also caught up with memories and traumas of war, betrayal, separation, and exodus. This article traces that history and illustrates how Vietnam's particular post-war refugee and remittance situations and channels illuminate networks and exacerbate inherent contradictions and comparisons in the mobile flows of finance, people, and goods across borders. Examining genealogies of remittance reception and management offers insight and intervention into analytical assumptions of the distancing and mediating functions inherent to classic conceptions of money, as well as the reciprocity and recognition perceptions mapped onto gift economies.
Folgezustände nach Hernienchirurgie: Was ist zu beachten?
Authors: Gerber Joël L. , Lavanchy Joël L. , Beldi Guido
Published: April 2020

Zusammenfassung. Da Hernienoperationen zunehmend ambulant durchgeführt werden, sind Hausärztinnen und Hausärzte vermehrt in die postoperative Betreuung involviert. Frühe sind von späten Folgezuständen nach Hernienchirurgie zu unterscheiden. Häufige frühpostoperative Probleme sind Hämatome, Serome und akute Schmerzen, wohingegen zu späteren Zeitpunkten Rezidive und potenziell chronifizierende Schmerzen im Vordergrund stehen. Dieser Übersichtsartikel zeigt Nachsorge, häufige postoperative Probleme und deren Therapieoptionen auf.
Redressing responses to the treatment gap for people with alcohol problems: The overlooked role of untreated remission from alcohol problems
Authors: Mellor Richard , Ritter Alison
Published: April 2020

Abstract. Aims: The “treatment gap” for people with alcohol problems has been identified as very large in the literature. An array of responses to the treatment gap have been focussed upon, including changing the perceptions of untreated people in order to make them want treatment more. A separate approach identifies the treatment system itself as the cause of the treatment gap. The aim of this paper was to consider research on untreated remission from alcohol problems to better understand responses to the treatment gap. Methodology: Three areas of existing published literature were thematically reviewed and synthesised: treatment gap research, untreated remission from alcohol problems research, and treatment planning and system design research. Results: Including rates of untreated remission from alcohol problems reduces the size of the treatment gap considerably. Treatment planning models which estimate unmet demand are better suited than unmet need when identifying gaps in service provision. Responding to the treatment gap requires broadening the treatment system beyond the specialised setting, and the assumptions associated with the process and expected outcomes of remission may need revisiting. Conclusions: Treatment planning models are useful when identifying gaps in service provision, but more sophisticated inclusion of untreated remission data is required. The treatment response may need to be diversified to support the life circumstances and perspectives of people with alcohol problems, with one example (outlined in this paper) being the provision of digital support services.
Stabile Präferenz oder flexibel am Diagnoseziel orientiert? – Die Bezugsnormwahl angehender Lehrkräfte
Authors: Lintorf Katrin , Buch Susanne R.
Published: April 2020

Zusammenfassung. Die Wahl von Vergleichsmaßstäben (Bezugsnormen) bei der Leistungsbeurteilung wurde bislang hauptsächlich unter der Perspektive einer relativ stabilen, situationsübergreifenden Präferenz erforscht. Nur wenige Studien untersuchten, ob die Wahl eines Vergleichsmaßstabs in Abhängigkeit vom Beurteilungsziel variiert. Masterstudierende ( N = 58) des Lehramts bearbeiteten daher die Kleine Beurteilungsaufgabe (KBA), eine handlungsnahe Erfassung der Bezugsnormorientierung, jeweils unter drei Zielvorgaben. Neben einer Kontrollbedingung (A) wurden mit einem Modifikationsziel (B) und einem Selektionsziel (C) zwei Kontexte realisiert, die unterschiedliche Bezugsnormwahlen nahelegen. Zusätzlich wurden die Studierenden zur Nutzung unterschiedlicher Vergleichsinformationen bei der Beurteilung befragt. In den Beurteilungen unter der Kontrollbedingung dominierte die soziale Bezugsnorm. In den Beurteilungen unter Kontext B und C dagegen war erwartungsgemäß die je nach Kontext zieladäquate Bezugsnorm besonders ausgeprägt. Allerdings zeigte sich hier ebenso eine zielunabhängige Dominanz der sozialen Bezugsnorm. Selbstauskünfte über die bei der Bewertung genutzten Vergleiche lassen vermuten, dass die Wahl der individuellen Bezugsnorm intentional geschieht, die der sozialen Bezugsnorm dagegen nicht-intentional. Die Befunde werden vor dem Hintergrund der Anforderungen an eine professionelle pädagogische Diagnostik diskutiert.
Kinder- und jugendpsychiatrische stationsäquivalente Behandlung (StäB): Therapieoption – für alle oder für wenige?
Authors: Boege Isabel , Schepker Renate , Grupp Dieter , Fegert Jörg M.
Published: April 2020

Zusammenfassung. Fragestellung: Aufsuchende stationsäquivalente Behandlung (StäB) ist seit dem 01.01.2017 in Deutschland möglich und seit dem 01.01.2018 abrechenbar. Dennoch wird StäB unter Infragestellung der Machbarkeit der Rahmenbedingungen derzeit nur an wenigen Standorten der Kinder- und Jugendpsychiatrie und Psychotherapie in Deutschland regelhaft angeboten. Ziel war es, anhand der ersten 58 stationsäquivalent behandelten Kinder und Jugendlichen am ZfP Südwürttemberg (2018–2019) die Machbarkeit und Kosten von StäB zu evaluieren. Methodik: Es wurden alle seit dem 01.01.2018 konsekutiv stationsäquivalent behandelten Fälle eingeschlossen und anhand von rein deskriptiven Analysen in SPSS.25 evaluiert. Ergebnisse: Die durchschnittliche Behandlungsdauer betrug 37.95 Tage (SD 15.35), 86.2 % aller Familien beendeten die Behandlung regelgerecht, es kam nur bei drei Patientinnen und Patienten zu einem einvernehmlichen Behandlungsabbruch, fünf mussten in eine stationäre Behandlung verlegt werden. Es wurden primär internalisierende Störungen indiziert (70.7 %), während externalisierende Störungen nur ein Viertel der Behandlungsfälle ausmachten (27.8 %). Kosten einer StäB beliefen sich im Durchschnitt auf 8779,25 €. Schlussfolgerungen: StäB stellt eine neue Behandlungsform im familiären Umfeld dar, welche täglich stattfindet. Multiprofessionalität der Behandlung ist Voraussetzung. Eine Umsetzung in den gegebenen Rahmenbedingungen ist möglich. Eine Akzeptanz von den Familien ist gegeben, die durchschnittliche Behandlungsdauer liegt leicht über dem stationären Bundesdurchschnitt.
Substanzbezogene Störungen im Jugend- und jungen Erwachsenenalter
Authors: Thomasius Rainer , Arnaud Nicolas , Holtmann Martin , Kiefer Falk
Published: April 2020

Zusammenfassung. Das Jugendalter ist eine besonders kritische Lebensphase für die Entwicklung von Suchterkrankungen und komorbiden psychischen Störungen. Substanzbezogene Störungen gehören zu den am weitesten verbreiteten psychischen Störungen im Jugend- und jungen Erwachsenenalter und sind in dieser Gruppe mit steigender Tendenz der häufigste Anlass für eine Krankenhausbehandlung. Dennoch fehlt es an jugendspezifischen Versorgungseinrichtungen und Kapazitäten für die qualifizierte Entzugsbehandlung für Jugendliche. Einrichtungen der medizinischen Rehabilitation fehlen fast vollständig. Im Hinblick auf die Versorgung von Adoleszenten mit substanzbezogenen Störungen unter einer lebenszeitlichen Perspektive ist die Schnittstelle zwischen Kinder- und Jugendpsychiatrie, Erwachsenenpsychiatrie und Psychotherapie mit der somatischen und psychosomatischen Medizin und der Suchthilfe relevant, da es sich bei den Suchterkrankungen häufig um zur Chronifizierung neigende und langjährig andauernde Krankheitsprozesse mit einer hohen Transmissionsrate handelt. Notwendig sind vernetzte Versorgungsstrukturen für Adoleszente an den Schnittstellen von Kinder- und Jugend- zur Erwachsenenpsychiatrie, die dem Entwicklungsstand und den pädagogischen Entwicklungsanforderungen junger Menschen und dem vielfach aufgrund von psychischer Komorbidität bestehenden psychotherapeutischen Behandlungsbedarf Rechnung trägt. Minderjährige nehmen Hilfen meist nicht aus eigener Initiative in Anspruch. Eine Begleitung der Transition durch vernetzte Angebote bei eindeutiger Regelung von Kostenzuständigkeit ist erforderlich. Eine (eigene) medizinische Rehabilitation und deren modellhafte Erprobung stellt eine empfehlenswerte Erweiterung des Behandlungsangebotes für suchtkranke Jugendliche dar.
Führt das Bewusstsein moralischer Grundwerte zu einem authentischeren Antwortverhalten in Beschwerdenvalidierungstests?
Authors: Kobelt-Pönicke Axel , Walter Franziska , Riemann Mario
Published: April 2020

Zusammenfassung. Hintergrund: Menschen rechtfertigen unehrliches Verhalten, um das subjektive Selbstbild nicht zu gefährden. Die Rechtfertigung muss dabei so überzeugend sein, dass moralische Grundwerte in den Hintergrund treten. Der hohe Anteil auffälliger Beschwerdenvalidierungstests in Begutachtungssituationen weist darauf hin, dass die subjektive Überzeugung, keiner Arbeitstätigkeit mehr nachgehen zu können, die moralische Verpflichtung zur authentischen Beschwerdenschilderung außer Kraft setzt. Fragestellung: Führt die Bewusstmachung moralischer, an Gerechtigkeit und Ehrlichkeit orientierter Werte zu Beginn einer sozialmedizinischen Begutachtung zu einer Verringerung unehrlichen Antwortverhaltens in Beschwerdenvalidierungstests? Methode: 93 Rentenantragsteller_innen wurden auf zwei Begutachtungsarme (mit und ohne Aktualisierung moralischer Werte vor der Bearbeitung von Beschwerdevalidierungstests (SFSS, BEVA) randomisiert. Ergebnisse: Die Bewusstmachung moralischer Werte, die an Gerechtigkeit, Ehrlichkeit und Rechtsempfinden appellieren, wirkte sich auf den BEVA, nicht jedoch auf den SFSS aus. Schlussfolgerung: Die Bewusstmachung moralischer Werte fördert ein authentisches Antwortverhalten. Der Effekt ist möglicherweise vom Grad des individuellen Bewusstseins über das eigene Täuschungsverhalten abhängig.
Influence of Elastic Scattering on Electron Swarm Distribution in Electrified Gases
Authors: Schmalzried A. , Luque A.
Published: April 2020

The propagation of energetic electrons through air is one key component in the generation of high‐energy atmospheric phenomena such as lightning‐generated X‐ray bursts, terrestrial gamma ray flashes (TGFs), and gamma ray glows. We show here that models for this propagation can be considerably affected by the parameterization of the differential cross section of elastic scattering of electrons on the molecular components of air. We assess existing parameterizations and propose a more accurate one that builds upon the most up‐to‐date measurements. Then we conclude that by overweighting the forward scattering probability, previous works may have overestimated the production of runaway electrons under high electric fields close to the thermal runaway threshold.
CSO Reduction by Integrated Model Predictive Control of Stormwater Inflows: A Simulated Proof of Concept Using Linear Surrogate Models
Authors: Lund N. S. V. , Borup M. , Madsen H. , Mark O. , Mikkelsen P. S.
Published: April 2020

Combined sewer overflows (CSO) of mixed stormwater and wastewater pollute nearby receiving surface waters and pose a risk to the environment and human health. We use “integrated stormwater inflow control” to mitigate CSO by dynamically controlling the inflow of stormwater to the combined sewer system in real time, expanding the physical space of traditional real‐time control. This control is carried out with model predictive control (MPC), which we base on convex optimization including a linear internal surrogate model of the controllable aboveground and belowground infrastructure. A detailed hydrodynamic model is used to evaluate the results and recursively initialize the surrogate model. MPC dynamically decides when to let stormwater enter the sewer system and when to store and convey excess stormwater in the aboveground infrastructure otherwise intended for passive cloudburst management. The performance was quantified in a simulation study in Copenhagen, Denmark, using a 1‐D distributed hydrodynamic model and 32 rain events from 2016, of which 18 caused CSO in the situation without control. Four of the 18 CSO events were avoided with MPC, and the total CSO volume was reduced by 98.4% of the potential reducible volume. For one event, stormwater was unnecessarily kept on the surface because the surrogate model wrongly predicted a CSO. The computational cost was in all cases compatible with an operational implementation. With the invention of proper actuators for control of stormwater inflows, we show that MPC of stormwater inflows may be a viable supplement to more traditional passive ways of managing stormwater in urban areas.
Use and abuse of dietary supplements in persons with diabetes
Authors: Hannon Bridget A. , Fairfield William D. , Adams Bryan , Kyle Theodore , Crow Mason , Thomas Diana M.
Published: April 2020

The dietary supplement industry has estimated sales of over $30 billion in the US and over $100 billion globally. Many consumers believe that dietary supplements are safer and possibly more effective than drugs to treat diabetes. The sheer volume of the literature in this space makes compiling them into one review challenging, so much so that primarily narrative reviews currently exist. By applying the interactive database supplied by the Office of Dietary Supplements at the National Institutes of Health, we identified the top 100 ingredients that appeared most often in dietary supplement products. One-hundred different keyword searches using the ingredient name and the word diabetes were performed using a program developed to automatically scrape PubMed. Each search was retained in a separate Excel spreadsheet, which was then reviewed for inclusion or exclusion. The studies that met the inclusion criteria were evaluated for effect of reducing and controlling diabetes. The PubMed scrape resulted in 6217 studies. For each keyword search only the most recent 100 were retained, which refined the total to 1823 studies. Of these 425 met the screening criteria. The ingredients, fiber, selenium and zinc had the most studies associated with improvement in diabetes. Several popular supplement ingredients (phosphorus, pantothenic acid, calcium, magnesium, glutamine, isoleucine, tyrosine, choline, and creatine monohydrate) did not result in any studies meeting our screening criteria. Our study demonstrates how to automate reviews to filter and collapse literature in content areas that have an enormous volume of studies. The aggregated set of studies suggest there is little clinical evidence for the use of dietary supplements to reduce or control diabetes.
Psychotic-like experiences, polygenic risk scores for schizophrenia, and structural properties of the salience, default mode, and central-executive networks in healthy participants from UK Biobank
Authors: Alloza C. , Blesa-Cábez M. , Bastin M. E. , Madole J. W. , Buchanan C. R. , Janssen J. , Gibson J. , Deary I. J. , Tucker-Drob E. M. , Whalley H. C. , Arango C. , McIntosh A. M. , Cox S. R. , Lawrie S. M.
Published: April 2020

Schizophrenia is a highly heritable disorder with considerable phenotypic heterogeneity. Hallmark psychotic symptoms can be considered as existing on a continuum from non-clinical to clinical populations. Assessing genetic risk and psychotic-like experiences (PLEs) in non-clinical populations and their associated neurobiological underpinnings can offer valuable insights into symptom-associated brain mechanisms without the potential confounds of the effects of schizophrenia and its treatment. We leveraged a large population-based cohort (UKBiobank,N = 3875) including information on PLEs (obtained from the Mental Health Questionnaire (MHQ); UKBiobank Category: 144;Nauditory hallucinations = 55,Nvisual hallucinations = 79,Npersecutory delusions = 16,Ndelusions of reference = 13), polygenic risk scores for schizophrenia (PRSSZ) and multi-modal brain imaging in combination with network neuroscience. Morphometric (cortical thickness, volume) and water diffusion (fractional anisotropy) properties of the regions and pathways belonging to the salience, default-mode, and central-executive networks were computed. We hypothesized that these anatomical concomitants of functional dysconnectivity would be negatively associated with PRSSZand PLEs. PRSSZwas significantly associated with a latent measure of cortical thickness across the salience network (r = −0.069,p = 0.010) and PLEs showed a number of significant associations, both negative and positive, with properties of the salience and default mode networks (involving the insular cortex, supramarginal gyrus, and pars orbitalis,pFDR < 0.050); with the cortical thickness of the insula largely mediating the relationship between PRSSZand auditory hallucinations. Generally, these results are consistent with the hypothesis that higher genetic liability for schizophrenia is related to subtle disruptions in brain structure and may predispose to PLEs even among healthy participants. In addition, our study suggests that networks engaged during auditory hallucinations show structural associations with PLEs in the general population.
DuoHexaBody-CD37®, a novel biparatopic CD37 antibody with enhanced Fc-mediated hexamerization as a potential therapy for B-cell malignancies
Authors: Oostindie Simone C. , van der Horst Hilma J. , Kil Laurens P. , Strumane Kristin , Overdijk Marije B. , van den Brink Edward N. , van den Brakel Jeroen H. N. , Rademaker Hendrik J. , van Kessel Berris , van den Noort Juliette , Chamuleau Martine E. D. , Mutis Tuna , Lindorfer Margaret A. , Taylor Ronald P. , Schuurman Janine , Parren Paul W. H. I. , Beurskens Frank J. , Breij Esther C. W.
Published: April 2020

Tetraspanin CD37 has recently received renewed interest as a therapeutic target for B-cell malignancies. Although complement-dependent cytotoxicity (CDC) is a powerful Fc-mediated effector function for killing hematological cancer cells, CD37-specific antibodies are generally poor inducers of CDC. To enhance CDC, the E430G mutation was introduced into humanized CD37 monoclonal IgG1 antibodies to drive more efficient IgG hexamer formation through intermolecular Fc-Fc interactions after cell surface antigen binding. DuoHexaBody-CD37, a bispecific CD37 antibody with the E430G hexamerization-enhancing mutation targeting two non-overlapping epitopes on CD37 (biparatopic), demonstrated potent and superior CDC activity compared to other CD37 antibody variants evaluated, in particular ex vivo in patient-derived chronic lymphocytic leukemia cells. The superior CDC potency was attributed to enhanced IgG hexamerization mediated by the E430G mutation in combination with dual epitope targeting. The mechanism of action of DuoHexaBody-CD37 was shown to be multifaceted, as it was additionally capable of inducing efficient antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis in vitro. Finally, potent anti-tumor activity in vivo was observed in cell line- and patient-derived xenograft models from different B-cell malignancy subtypes. These encouraging preclinical results suggest that DuoHexaBody-CD37 (GEN3009) may serve as a potential therapeutic antibody for the treatment of human B-cell malignancies.
DNA methylation and copy number variation profiling of T-cell lymphoblastic leukemia and lymphoma
Authors: Haider Zahra , Landfors Mattias , Golovleva Irina , Erlanson Martin , Schmiegelow Kjeld , Flægstad Trond , Kanerva Jukka , Norén-Nyström Ulrika , Hultdin Magnus , Degerman Sofie
Published: April 2020

Despite having common overlapping immunophenotypic and morphological features, T-cell lymphoblastic leukemia (T-ALL) and lymphoma (T-LBL) have distinct clinical manifestations, which may represent separate diseases. We investigated and compared the epigenetic and genetic landscape of adult and pediatric T-ALL (n = 77) and T-LBL (n = 15) patient samples by high-resolution genome-wide DNA methylation and Copy Number Variation (CNV) BeadChip arrays. DNA methylation profiling identified the presence of CpG island methylator phenotype (CIMP) subgroups within both pediatric and adult T-LBL and T-ALL. An epigenetic signature of 128 differentially methylated CpG sites was identified, that clustered T-LBL and T-ALL separately. The most significant differentially methylated gene loci included the SGCE/PEG10 shared promoter region, previously implicated in lymphoid malignancies. CNV analysis confirmed overlapping recurrent aberrations between T-ALL and T-LBL, including 9p21.3 (CDKN2A/CDKN2B) deletions. A significantly higher frequency of chromosome 13q14.2 deletions was identified in T-LBL samples (36% in T-LBL vs. 0% in T-ALL). This deletion, encompassing the RB1, MIR15A and MIR16-1 gene loci, has been reported as a recurrent deletion in B-cell malignancies. Our study reveals epigenetic and genetic markers that can distinguish between T-LBL and T-ALL, and deepen the understanding of the biology underlying the diverse disease localization.
Oxidative resistance of leukemic stem cells and oxidative damage to hematopoietic stem cells under pro-oxidative therapy
Authors: Chen Yongfeng , Liang Yong , Luo Xingjing , Hu Qiongying
Published: April 2020

Leukemic stem cells (LSCs) and hematopoietic stem cells (HSCs) are both dependent on the hypoxic bone marrow (BM) microenvironment (also known as the BM niche). There is always fierce competition between the two types of cells, and the former exhibits a greater competitive advantage than the latter via multiple mechanisms. Under hypoxia, the dynamic balance between the generation and clearing of intracellular reactive oxygen species (ROS) is conducive to maintaining a quiescent state of cells. Quiescent LSCs can reside well in the BM niche, avoiding attack by chemotherapeutic agents, which is the cause of chemotherapeutic resistance and relapse in leukemia. HSCs acquire energy mainly through anaerobic glycolysis, whereas LSCs achieve energy metabolism largely through mitochondrial oxidative respiration. Mitochondria are the primary site of ROS generation. Thus, in theory, mitochondria-mediated respiration will cause an increase in ROS generation in LSCs and a higher intracellular oxidative stress level. The sensitivity of the cells to pro-oxidant drugs increases as well, which allows for the selective clearing of LSCs by pro-oxidative therapy. However, HSCs are also highly sensitive to changes in ROS levels, and the toxic effects of pro-oxidant drugs on HSCs poses a major challenge to pro-oxidative therapy in leukemia. Given the above facts, we reviewed studies on the oxidative resistance of LSCs and the oxidative damage to HSCs under pro-oxidative therapy. An in-depth investigation into the oxidative stress status and regulatory mechanisms of LSCs and HSCs in hypoxic environments will promote our understanding of the survival strategy employed by LSCs and the mechanism of the oxidative damage to HSCs in the BM niche, thus facilitating individualized treatment of leukemia patients and helping eliminate LSCs without disturbing normal hematopoietic cells.
CD41-deficient exosomes from non-traumatic femoral head necrosis tissues impair osteogenic differentiation and migration of mesenchymal stem cells
Authors: Zhu Weiwen , Guo MinKang , Yang Wu , Tang Min , Chen Tingmei , Gan Delu , Zhang Dian , Ding Xiaojuan , Zhao Anping , Zhao Pei , Yan Wenlong , Zhang Jian
Published: April 2020

Non-traumatic osteonecrosis of the femoral head (ONFH) is clinically a devastating and progressive disease without an effective treatment. Mesenchymal stem cells (MSCs) transplantation has been used to treat ONFH in early stage, but the failure rate of this therapy is high due to the reduced osteogenic differentiation and migration of the transplanted MSCs related with pathological bone tissues. However, the mechanism responsible for this decrease is still unclear. Therefore, we assume that the implanted MSCs might be influenced by signals delivered from pathological bone tissue, where the exosomes might play a critical role in this delivery. This study showed that exosomes from ONFH bone tissues (ONFH-exos) were able to induce GC-induced ONFH-like damage, in vivo and impair osteogenic differentiation and migration of MSCs, in vitro. Then, we analyzed the differentially expressed proteins (DEPs) in ONFH-exos using proteomic technology and identified 842 differentially expressed proteins (DEPs). On the basis of gene ontology (GO) enrichment analysis of DEPs, fold-changes and previous report, cell adhesion-related CD41 (integrin α2b) was selected for further investigation. Our study showed that the CD41 (integrin α2b) was distinctly decreased in ONFH-exos, compared to NOR-exos, and downregulation of CD41 could impair osteogenic differentiation and migration of the MSCs, where CD41-integrin β3-FAK-Akt-Runx2 pathway was involved. Finally, our study further suggested that CD41-affluent NOR-exos could restore the glucocorticoid-induced decline of osteogenic differentiation and migration in MSCs, and prevent GC-induced ONFH-like damage in rat models. Taken together, our study results revealed that in the progress of ONFH, exosomes from the pathological bone brought about the failure of MSCs repairing the necrotic bone for lack of some critical proteins, like integrin CD41, and prompted the progression of experimentally induced ONFH-like status in the rat. CD41 could be considered as the target of early diagnosis and therapy in ONFH.
Elimination of senescent cells by β-galactosidase-targeted prodrug attenuates inflammation and restores physical function in aged mice
Authors: Cai Yusheng , Zhou Huanhuan , Zhu Yinhua , Sun Qi , Ji Yin , Xue Anqi , Wang Yuting , Chen Wenhan , Yu Xiaojie , Wang Longteng , Chen Han , Li Cheng , Luo Tuoping , Deng Hongkui
Published: April 2020

Cellular senescence, a persistent state of cell cycle arrest, accumulates in aged organisms, contributes to tissue dysfunction, and drives age-related phenotypes. The clearance of senescent cells is expected to decrease chronic, low-grade inflammation and improve tissue repair capacity, thus attenuating the decline of physical function in aged organisms. However, selective and effective clearance of senescent cells of different cell types has proven challenging. Herein, we developed a prodrug strategy to design a new compound based on the increased activity of lysosomal β-galactosidase (β-gal), a primary characteristic of senescent cells. Our prodrug SSK1 is specifically activated by β-gal and eliminates mouse and human senescent cells independently of senescence inducers and cell types. In aged mice, our compound effectively cleared senescent cells in different tissues, decreased the senescence- and age-associated gene signatures, attenuated low-grade local and systemic inflammation, and restored physical function. Our results demonstrate that lysosomal β-gal can be effectively leveraged to selectively eliminate senescent cells, providing a novel strategy to develop anti-aging interventions.
Targeted delivery of nanomaterials with chemical cargoes in plants enabled by a biorecognition motif
Authors: Santana Israel , Wu Honghong , Hu Peiguang , Giraldo Juan Pablo
Published: April 2020

Current approaches for nanomaterial delivery in plants are unable to target specific subcellular compartments with high precision, limiting our ability to engineer plant function. We demonstrate a nanoscale platform that targets and delivers nanomaterials with biochemicals to plant photosynthetic organelles (chloroplasts) using a guiding peptide recognition motif. Quantum dot (QD) fluorescence emission in a low background window allows confocal microscopy imaging and quantitative detection by elemental analysis in plant cells and organelles. QD functionalization with β-cyclodextrin molecular baskets enables loading and delivery of diverse chemicals, and nanoparticle coating with a rationally designed and conserved guiding peptide targets their delivery to chloroplasts. Peptide biorecognition provides high delivery efficiency and specificity of QD with chemical cargoes to chloroplasts in plant cells in vivo (74.6 ± 10.8%) and more specific tunable changes of chloroplast redox function than chemicals alone. Targeted delivery of nanomaterials with chemical cargoes guided by biorecognition motifs has a broad range of nanotechnology applications in plant biology and bioengineering, nanoparticle-plant interactions, and nano-enabled agriculture.
Bidimensional lamellar assembly by coordination of peptidic homopolymers to platinum nanoparticles
Authors: Manai Ghada , Houimel Hend , Rigoulet Mathilde , Gillet Angélique , Fazzini Pier-Francesco , Ibarra Alfonso , Balor Stéphanie , Roblin Pierre , Esvan Jérôme , Coppel Yannick , Chaudret Bruno , Bonduelle Colin , Tricard Simon
Published: April 2020

A key challenge for designing hybrid materials is the development of chemical tools to control the organization of inorganic nanoobjects at low scales, from mesoscopic (~µm) to nanometric (~nm). So far, the most efficient strategy to align assemblies of nanoparticles consists in a bottom-up approach by decorating block copolymer lamellae with nanoobjects. This well accomplished procedure is nonetheless limited by the thermodynamic constraints that govern copolymer assembly, the entropy of mixing as described by the Flory–Huggins solution theory supplemented by the critical influence of the volume fraction of the block components. Here we show that a completely different approach can lead to tunable 2D lamellar organization of nanoparticles with homopolymers only, on condition that few elementary rules are respected: 1) the polymer spontaneously allows a structural preorganization, 2) the polymer owns functional groups that interact with the nanoparticle surface, 3) the nanoparticles show a surface accessible for coordination.
Endothelial E-selectin inhibition improves acute myeloid leukaemia therapy by disrupting vascular niche-mediated chemoresistance
Authors: Barbier Valerie , Erbani Johanna , Fiveash Corrine , Davies Julie M. , Tay Joshua , Tallack Michael R. , Lowe Jessica , Magnani John L. , Pattabiraman Diwakar R. , Perkins Andrew C. , Lisle Jessica , Rasko John E. J. , Levesque Jean-Pierre , Winkler Ingrid G.
Published: April 2020

The endothelial cell adhesion molecule E-selectin is a key component of the bone marrow hematopoietic stem cell (HSC) vascular niche regulating balance between HSC self-renewal and commitment. We now report in contrast, E-selectin directly triggers signaling pathways that promote malignant cell survival and regeneration. Using acute myeloid leukemia (AML) mouse models, we show AML blasts release inflammatory mediators that upregulate endothelial niche E-selectin expression. Alterations in cell-surface glycosylation associated with oncogenesis enhances AML blast binding to E-selectin and enable promotion of pro-survival signaling through AKT/NF-κB pathways. In vivo AML blasts with highest E-selectin binding potential are 12-fold more likely to survive chemotherapy and main contributors to disease relapse. Absence (in Sele−/− hosts) or therapeutic blockade of E-selectin using small molecule mimetic GMI-1271/Uproleselan effectively inhibits this niche-mediated pro-survival signaling, dampens AML blast regeneration, and strongly synergizes with chemotherapy, doubling the duration of mouse survival over chemotherapy alone, whilst protecting endogenous HSC.
Engineered niches support the development of human dendritic cells in humanized mice
Authors: Anselmi Giorgio , Vaivode Kristine , Dutertre Charles-Antoine , Bourdely Pierre , Missolo-Koussou Yoann , Newell Evan , Hickman Oliver , Wood Kristie , Saxena Alka , Helft Julie , Ginhoux Florent , Guermonprez Pierre
Published: April 2020

Classical dendritic cells (cDCs) are rare sentinel cells specialized in the regulation of adaptive immunity. Modeling cDC development is crucial to study cDCs and harness their therapeutic potential. Here we address whether cDCs could differentiate in response to trophic cues delivered by mesenchymal components of the hematopoietic niche. We find that mesenchymal stromal cells engineered to express membrane-bound FLT3L and stem cell factor (SCF) together with CXCL12 induce the specification of human cDCs from CD34+hematopoietic stem and progenitor cells (HSPCs). Engraftment of engineered mesenchymal stromal cells (eMSCs) together with CD34+HSPCs creates an in vivo synthetic niche in the dermis of immunodeficient mice driving the differentiation of cDCs and CD123+AXL+CD327+pre/AS-DCs. cDC2s generated in vivo display higher levels of resemblance with human blood cDCs unattained by in vitro-generated subsets. Altogether, eMSCs provide a unique platform recapitulating the full spectrum of cDC subsets enabling their functional characterization in vivo.
Universally autonomous self-healing elastomer with high stretchability
Authors: Guo Hongshuang , Han Yi , Zhao Weiqiang , Yang Jing , Zhang Lei
Published: April 2020

Developing autonomous self-healing materials for applications in harsh conditions is challenging because the reconstruction of interaction in material for self-healing will experience significant resistance and fail. Herein, a universally self-healing and highly stretchable supramolecular elastomer is designed by synergistically incorporating multi-strength H-bonds and disulfide metathesis in polydimethylsiloxane polymers. The resultant elastomer exhibits high stretchability for both unnotched (14000%) and notched (1300%) samples. It achieves fast autonomous self-healing under universal conditions, including at room temperature (10 min for healing), ultralow temperature (−40 °C), underwater (93% healing efficiency), supercooled high-concentrated saltwater (30% NaCl solution at −10 °C, 89% efficiency), and strong acid/alkali environment (pH = 0 or 14, 88% or 84% efficiency). These properties are attributable to synergistic interaction of the dynamic strong and weak H-bonds and stronger disulfide bonds. A self-healing and stretchable conducting device built with the developed elastomer is demonstrated, thereby providing a direction for future e-skin applications.
The BRCA2-MEILB2-BRME1 complex governs meiotic recombination and impairs the mitotic BRCA2-RAD51 function in cancer cells
Authors: Zhang Jingjing , Gurusaran Manickam , Fujiwara Yasuhiro , Zhang Kexin , Echbarthi Meriem , Vorontsov Egor , Guo Rui , Pendlebury Devon F. , Alam Intekhab , Livera Gabriel , Emmanuelle Martini , Wang P. Jeremy , Nandakumar Jayakrishnan , Davies Owen R. , Shibuya Hiroki
Published: April 2020

Breast cancer susceptibility gene II (BRCA2) is central in homologous recombination (HR). In meiosis, BRCA2 binds to MEILB2 to localize to DNA double-strand breaks (DSBs). Here, we identify BRCA2 and MEILB2-associating protein 1 (BRME1), which functions as a stabilizer of MEILB2 by binding to an α-helical N-terminus of MEILB2 and preventing MEILB2 self-association. BRCA2 binds to the C-terminus of MEILB2, resulting in the formation of the BRCA2-MEILB2-BRME1 ternary complex. In Brme1 knockout (Brme1−/−) mice, the BRCA2-MEILB2 complex is destabilized, leading to defects in DSB repair, homolog synapsis, and crossover formation. Persistent DSBs in Brme1−/− reactivate the somatic-like DNA-damage response, which repairs DSBs but cannot complement the crossover formation defects. Further, MEILB2-BRME1 is activated in many human cancers, and somatically expressed MEILB2-BRME1 impairs mitotic HR. Thus, the meiotic BRCA2 complex is central in meiotic HR, and its misregulation is implicated in cancer development.
Photonic curing of solution-deposited ZrO2 dielectric on PEN: a path towards high-throughput processing of oxide electronics
Authors: Daunis Trey B. , Schroder Kurt A. , Hsu Julia W. P.
Published: April 2020

High-throughput manufacturing of oxide electronics will enable new applications ranging from large-area displays to flexible medical devices and low-cost solar panels. However, high-quality oxide films from solution-based precursors typically require 20 min or more of thermal annealing at high temperature (>250 °C) for each layer, severely limiting both the throughput and substrate choice. Here, we report high-speed photonic curing of ZrO2dielectric thin films on flexible plastic substrates. The curing and patterning processes can be achieved simultaneously by using shadow mask patterning or adjusting conditions to convert oxide only on top of underlying metal contacts, i.e. self-aligned patterning. Metal–insulator–metal capacitors using two layers of ZrO2films photonically cured in just 100 s per layer show non-dispersive capacitance–frequency behaviour from 102to 106 Hz, high areal capacitance of 200 nF/cm2and low dissipation factor of 0.03 at 105 Hz, leakage current density of ~10−7 A/cm2at an applied field of 2 MV/cm, and a breakdown field of nearly 8 MV/cm. Using an upgraded tool, similar dielectric properties are achieved in as short as 100 ms using a single pulse of light, revealing a pathway to oxide film processing beyond 30 m/min.