bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of extended abstinence on cognitive functions in tramadol‐dependent patients: A cohort study
Authors: Hassaan Shehab H. , Khalifa Hossam , Darwish Alaa M.
Published: June 2021

Background

Some pieces of the literature report impaired cognitive functioning in tramadol dependence. Whether extended abstinence improves cognitive functioning or not is not well studied.

Aim

We aimed to measure the change in cognitive functioning following complete abstinence among individuals with tramadol dependence.

Methods

Eighty‐three male tramadol‐dependent (TD) and 57 matched healthy controls participated in this study. Cognitive functions were assessed using: The Trail making test (TMT), Wechsler Memory Scale‐Revised (WMS‐R), and Wechsler Adult Intelligence Scale (WAIS). Patients were assessed in the first week immediately after the end of the in‐patient treatment program (T1), and after six months of sustained abstinence (T2).

Results

At T1, the TD group showed deficits on all tested cognitive parameters (visual attention, task switching, working memory, visual memory, verbal memory, verbal knowledge, Verbal IQ, Performance IQ, and Full‐Scale IQ) in comparison to the control group. At T2, significant improvements had occurred in all the tested parameters except performance IQ. The cognitive performance of the abstinent individuals at T2 was comparable to the control group for the verbal subsets of WMS‐R, Verbal IQ, Performance IQ, and Full‐Scale IQ. Nevertheless, it was still worse than the control group in TMT, and all other WMS subsets.

Conclusion

tramadol dependence has negative effects on cognitive performance, which improves with extended abstinence.
Patient‐provider discussions of bariatric surgery and subsequent weight changes and receipt of bariatric surgery
Authors: Chang Lee‐Shing , Malmasi Shervin , Hosomura Naoshi , Zhang Huabing , Brown C. Justin , Lei Victor J. , Rubin Alexa , Ting Clara , Tong Kimhouy , Shubina Maria , Turchin Alexander
Published: June 2021

Objective

The purpose of this study was to determine whether patients who discuss bariatric surgery with their providers are more likely to undergo the procedure and to lose weight.

Methods

A retrospective cohort study of adults with BMI ≥ 35 kg/m2 treated between 2000 and 2015 was conducted to analyze the relationship between a discussion of bariatric surgery in the first year after study entry and weight changes (primary outcome) and receipt of bariatric surgery (secondary outcome) over 2 years after study entry. Natural language processing was used to identify the documentation of bariatric surgery discussion in electronic provider notes.

Results

Out of 30,560 study patients, a total of 2,659 (8.7%) discussed bariatric surgery with their providers. The BMI of patients who discussed bariatric surgery decreased by 2.18 versus 0.21 for patients who did not (p < 0.001). In a multivariable analysis, patients who discussed bariatric surgery with their providers lost more weight (by 1.43 [change in BMI]; 95% CI: 1.29‐1.57) and had greater odds (10.2; 95% CI: 9.0‐11.6; p < 0.001) of undergoing bariatric surgery.

Conclusions

Clinicians rarely discussed bariatric surgery with their patients. Patients who did have this discussion were more likely to lose weight and to undergo bariatric surgery.
A Phase I, First-in-Human Study of GSK2849330, an Anti-HER3 Monoclonal Antibody, in HER3-Expressing Solid Tumors
Authors: Gan Hui K. , Millward Michael , Jalving Mathilde , Garrido-Laguna Ignacio , Lickliter Jason D. , Schellens Jan H.M. , Lolkema Martijn P. , Van Herpen Carla L.M. , Hug Bruce , Tang Lihua , O'Connor-Semmes Robin , Gagnon Robert , Ellis Catherine , Ganji Gopinath , Matheny Christopher , Drilon Alexander
Published: June 2021

Background

GSK2849330, an anti-HER3 monoclonal antibody that blocks HER3/Neuregulin 1 (NRG1) signaling in cancer cells, is engineered for enhanced antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. This phase I, first-in-human, open-label study assessed the safety, pharmacokinetics (PK), pharmacodynamics, and preliminary activity of GSK2849330 in patients with HER3-expressing advanced solid tumors.

Patients and Methods

Patients with various tumor types were prospectively selected for HER3 expression by immunohistochemistry; a subset was also screened for NRG1 mRNA expression. In the dose-escalation phase, patients received GSK2849330 1.4–30 mg/kg every 2 weeks, or 3 mg/kg or 30 mg/kg weekly, intravenously (IV). In the dose-expansion phase, patients received 30 mg/kg GSK2849330 IV weekly.

Results

Twenty-nine patients with HER3-expressing cancers, of whom two expressed NRG1, received GSK2849330 (dose escalation: n = 18, dose expansion: n = 11). GSK2849330 was well tolerated. No dose-limiting toxicities were observed. The highest dose, of 30 mg/kg weekly, expected to provide full target engagement, was selected for dose expansion. Treatment-emergent adverse events (AEs) were mostly grade 1 or 2. The most common AEs were diarrhea (66%), fatigue (62%), and decreased appetite (31%). Dose-proportional plasma exposures were achieved, with evidence of HER3 inhibition in paired tissue biopsies. Of 29 patients, only 1 confirmed partial response, lasting 19 months, was noted in a patient with CD74-NRG1-rearranged non-small cell lung cancer (NSCLC).

Conclusion

GSK2849330 demonstrated a favorable safety profile, dose-proportional PK, and evidence of target engagement, but limited antitumor activity in HER3-expressing cancers. The exceptional response seen in a patient with CD74-NRG1-rearranged NSCLC suggests further exploration in NRG1-fusion–positive cancers.

Implications for Practice

This first-in-human study confirms that GSK2849330 is well tolerated. Importantly, across a variety of HER3-expressing advanced tumors, prospective selection by HER3/NRG1 expression alone was insufficient to identify patients who could benefit from treatment with this antibody-dependent cell-mediated cytotoxicity– and complement-dependent cytotoxicity–enhanced anti-HER3 antibody. The only confirmed durable response achieved was in a patient with CD74-NRG1-rearranged lung cancer. This highlights the potential utility of screening for NRG1 fusions prospectively across tumor types to enrich potential responders to anti-HER3 agents in ongoing trials.
Participatory mapping reveals socioeconomic drivers of forest fires in protected areas of the post‐conflict Colombian Amazon
Authors: Tebbutt Charlie Arthur , Devisscher Tahia , Obando‐Cabrera Laura , Gutiérrez García Gustavo Adolfo , Meza Elizalde Maria Constanza , Armenteras Dolors , Oliveras Menor Imma
Published: June 2021

Wildfires have increased in protected areas (PAs) of the Colombian Amazon following the 2016 peace agreement between the Government and the Revolutionary Armed Forced of Colombia (FARC—Spanish acronym). Recent study efforts to understand this issue suffer from data scarcity and limited consultation of local stakeholder perspectives on factors affecting wildfires.

This study uses a social–ecological systems framework to investigate local perceptions of factors driving and/or preventing wildfires in the Los Picachos, La Macarena and Tinigua PAs, which are shared by two Amazonian departments experiencing wildfire increase. Four stakeholder categories were selected to represent varied and possibly conflicting interests: cattle ranchers, the national park service, local authorities and cross‐sectional stakeholders. We combined a participative mapping approach with interviews to illustrate stakeholder perceptions of interactions between key variables in graphical causal models. Network analyses were used to determine areas of agreement on key variables, and to compare local priorities with those of key informants at the national level.

Local stakeholders and key informants widely agreed on the roles of extensive cattle ranching and land grabbing as key drivers of wildfires. The analysis identified areas for further research into wildfire occurrence within PAs. These include lack of governance and untitled land, as well as the effects of poor access to basic public services on unsustainable ranching methods.

This study revealed contested opinions between ranchers and other stakeholders over interactions between ranching, roads and illicit crops, and consequently their effects on wildfire occurrence. This indicates the need for cautious implementation of the National Development Plan, prioritising road maintenance over expansion, integrating arable alternatives to cattle ranching and considering multiple stakeholders in regional decision‐making around wildfire reduction. The strengths and limitations of the participative mapping approach employed here are discussed with a view to aiding decision‐making in post‐conflict regions of the Global South.
Targeted mutation of transcription factor genes alters metaxylem vessel size and number in rice roots
Authors: Reeger Jenna E. , Wheatley Matthew , Yang Yinong , Brown Kathleen M.
Published: June 2021

Root metaxylem vessels are responsible for axial water transport and contribute to hydraulic architecture. Variation in metaxylem vessel size and number can impact drought tolerance in crop plants, including rice, a crop that is particularly sensitive to drought. Identifying and validating candidate genes for metaxylem development would aid breeding efforts for improved varieties for drought tolerance. We identified three transcription factor candidate genes that potentially regulate metaxylem vessel size and number in rice based on orthologous annotations, published expression data, and available root and drought‐related QTL data. Single gene knockout mutants were generated for each candidate using CRISPR‐Cas9 genome editing. Root metaxylem vessel area and number were analyzed in 6‐week‐old knockout mutants and wild‐type plants under well‐watered and drought conditions in the greenhouse. Compared with wild type, LONESOME HIGHWAY (OsLHW) mutants had fewer, smaller metaxylem vessels in shallow roots and more, larger vessels in deep roots in drought conditions, indicating that OsLHW may be a repressor of drought‐induced metaxylem plasticity. The AUXIN RESPONSE FACTOR 15 mutants showed fewer but larger metaxylem vessel area in well‐watered conditions, but phenotypes were inconsistent under drought treatment. ORYZA SATIVA HOMEBOX 6 (OSH6) mutants had fewer, smaller metaxylem vessels in well‐watered conditions with greater effects on xylem number than size. OSH6 mutants had larger shoots and more, deeper roots than the wild type in well‐watered conditions, but there were no differences in performance under drought between mutants and wild type. Though these candidate gene mutants did not exhibit large phenotypic effects, the identification and investigation of candidate genes related to metaxylem traits in rice deepen our understanding of metaxylem development and are needed to facilitate incorporation of favorable alleles into breeding populations to improve drought stress tolerance.
The molecular mechanism underlying pathogenicity inhibition by sanguinarine in Magnaporthe oryzae
Authors: Anjago Wilfred Mabeche , Zeng Wenlong , Chen Yixiao , Wang Yupeng , Biregeya Jules , Li Yunxi , Zhang Tian , Peng Minghui , Cai Yan , Shi Mingyue , Wang Baohua , Zhang Dongmei , Wang Zonghua , Chen Meilian
Published: June 2021

BACKGROUND

Sanguinarine (SAN) is a benzophenanthridine alkaloid that broadly targets a range of pathways in mammalian and fungal cells. In this study we set out to explore the molecular mechanism of sanguinarine inhibition of the fungal development and pathogenicity of Magnaporthe oryzae with the hope that sanguinarine will bolster the development of antiblast agents.

RESULTS

We found that the fungus exhibited a significant reduction in vegetative growth and hyphal melanization while the spores produced long germ tubes on the artificial hydrophobic surface characteristic of a defect in thigmotropic sensing when exposed to 4, 8 and 0.5 μm sanguinarine, respectively. Consistent with these findings, we observed that the genes involved in melanin biosynthesis and the fungal hydrophobin MoMPG1 were remarkably suppressed in mycelia treated with 8 μm sanguinarine. Additionally, sanguinarine inhibited appressorium formation at a dose of 1.0 μm and this defect was restored by supplementing 5 mM of exogenous cAMP. By qRT‐PCR assay we found cAMP pathway signalling genes such as MoCAP1 and MoCpkA were significantly repressed whereas MoCDTF1 and MoSOM1 were upregulated in sanguinarine‐treated strains. Furthermore, we showed that sanguinarine does not selectively inhibit vegetative growth and appressorium formation of Guy11 but also other strains of M. oryzae. Finally, treatment of sanguinarine impaired the appressorium‐mediated penetration and pathogenicity of M. oryzae in a dose‐dependent manner.

CONCLUSION

Based on our results we concluded that sanguinarine is an attractive antimicrobial candidate for fungicide development in the control of rice blast disease. © 2021 Society of Chemical Industry.
Characterizing cancer‐associated myosteatosis: anatomic distribution and cancer‐specific variability of low radiodensity muscle
Authors: Armstrong Victoria , Stretch Cynthia , Fitzgerald Liam , Gopaul Aquila , McKinnon Greg , Koziak Jennifer , Kopciuk Karen , Brockton Nigel , Bathe Oliver F.
Published: June 2021

Background

Low muscle radiodensity on computed tomography (CT) scan, indicative of myosteatosis, is commonly observed in cancer patients and can be associated with poor prognosis. Radiodensity is typically measured at the level of the third lumbar vertebra (L3). It is unknown whether features at L3 reflect a systemic state affecting peripheral muscle groups, whether images used at different levels can be used as a surrogate if L3 images are unavailable, and how radiodensity varies between cancer types.

Methods

Core and extremity muscle radiodensities were measured in whole body CT images from melanoma patients to evaluate the anatomical distribution of muscle radiodensity measurements. Core muscle radiodensity was measured in 891 patients with different cancer types to study malignancy‐dependent patterns in muscle radiodensity.

Results

Low muscle radiodensity at L3 (<30 Hounsfield Unit) was associated with a corresponding lower muscle radiodensity in all muscle groups evaluated (P < 0.001). However, muscle radiodensities were lowest in the core muscle groups compared with muscles in the extremities. Muscle radiodensities at T12 closely correlated with measurements taken at L3 (r = 0.920, P < 0.001), but the correlation was weaker with mid‐thigh measurements (r = 0.745, P < 0.001). The distribution of muscle radiodensities varied significantly with cancer type (P = 0.002).

Conclusions

The uniform distribution of low muscle radiodensity in cancer patients supports the hypothesis that the underlying mechanism for myosteatosis is systemic in nature. The most reliable measurements of muscle radiodensity are taken using images of core muscles. Variations in muscle radiodensity associated with cancer exist, suggesting that cancer‐specific biological drivers are at play.
Observer‐based adaptive neural networks control for Markovian jump nonlinear systems with partial mode information and input saturation
Authors: Cao Boqiang , Nie Xiaobing
Published: June 2021

The observer‐based adaptive neural networks control problem is studied in this article for nonlinear Markovian jump systems (MJSs) with partial mode information and input saturation. The existing adaptive control scheme for MJSs works only when the Markov mode of system is completely known. For this reason, the concept of partial mode information of Markov chain is embedded into the framework of adaptive backstepping method and then a mode detector is set to emit the mode. To achieve the control objective, only the emitted mode is used to design the state observer and adaptive control scheme. Besides, an auxiliary signal is introduced in MJSs to compensate the effect of input saturation and this signal appears in controller as the input of neural networks instead of a separate term, which makes the form of proposed controller simpler than that in the literature. Finally, a numerical example and a practical example are provided to demonstrate the feasibility of our control scheme.
Analysis of covariance under variance heteroscedasticity in general factorial designs
Authors: Konietschke Frank , Cao Cong , Gunawardana Asanka , Zimmermann Georg
Published: June 2021

Adjusting for baseline values and covariates is a recurrent statistical problem in medical science. In particular, variance heteroscedasticity is non‐negligible in experimental designs and ignoring it might result in false conclusions. Approximate inference methods are developed to test null hypotheses formulated in terms of adjusted treatment effects and regression parameters in general analysis of covariance designs with arbitrary numbers of factors. Variance homoscedasticity is not assumed. The distributions of the test statistics are approximated using Box‐type approximation methods. Extensive simulation studies show that the procedures are particularly suitable when sample sizes are rather small. A real data set illustrates the application of the methods.
Mobility Extraction in 2D Transition Metal Dichalcogenide Devices—Avoiding Contact Resistance Implicated Overestimation
Authors: Pang Chin‐Sheng , Zhou Ruiping , Liu Xiangkai , Wu Peng , Hung Terry Y. T. , Guo Shiqi , Zaghloul Mona E. , Krylyuk Sergiy , Davydov Albert V. , Appenzeller Joerg , Chen Zhihong
Published: June 2021

Schottky barrier (SB) transistors operate distinctly different from conventional metal‐oxide semiconductor field‐effect transistors, in a unique way that the gate impacts the carrier injection from the metal source/drain contacts into the channel region. While it has been long recognized that this can have severe implications for device characteristics in the subthreshold region, impacts of contact gating of SB in the on‐state of the devices, which affects evaluation of intrinsic channel properties, have been yet comprehensively studied. Due to the fact that contact resistance (RC) is always gate‐dependent in a typical back‐gated device structure, the traditional approach of deriving field‐effect mobility from the maximum transconductance (gm) is in principle not correct and can even overestimate the mobility. In addition, an exhibition of two different threshold voltages for the channel and the contact region leads to another layer of complexity in determining the true carrier concentration calculated from Q = COX * (VG–VTH). Through a detailed experimental analysis, the effect of different effective oxide thicknesses, distinct SB heights, and doping‐induced reductions in the SB width are carefully evaluated to gain a better understanding of their impact on important device metrics.
Evolutionary pattern ofMetacaremysgen. nov. (Rodentia, Octodontidae) and its biochronological implications for the late Miocene and early Pliocene of southern South America
Authors: Piñero Pedro , Verzi Diego H. , Olivares A. Itatí , Montalvo Claudia I. , Tomassini Rodrigo L. , Fernández Villoldo Ariel
Published: June 2021

We analyse the taxonomic status and diversity of the late Miocene Octodontoidea (Hystricognathi)Cercomys primitivaand related samples, a taxon previously known only from the holotype specimen. New findings associated with an extensive review of late Miocene and early Pliocene rodents have allowed us to recognize the occurrence of this and other related species in several localities of central and western Argentina, and in south‐central Bolivia. We discuss the invalidity ofCercomysand propose the new genusMetacaremys, which includes the type speciesMetacaremys primitivacomb. nov. and two new species,Metacaremys calfucalelsp. nov. andMetacaremys dimisp. nov. Osteological, brain and dental morphology show that the new genus is not related to Brazilian Echimyidae, as previously considered, but to the southern family Octodontidae. Although the molar morphology of this genus is quite conservative, comparison of the samples shows a variation in size. We discuss the plausible evolutionary pattern explaining this variation and the implied biochronological and biostratigraphical information. It is recognized as an anagenetic lineage in which an increase in size occurs from the oldest species,M. primitivacomb. nov. (early late Miocene,c. 9.23 Ma), to the youngest species,M. dimisp. nov. (Miocene–Pliocene boundary,c. 5.28 Ma).Metacaremys calfucalelis intermediate in size and age between these two species. The polarity of this pattern of change is consistent with that shown by other partially synchronous independent lineages of octodontoids, thus providing new evidence for the biochronological and biostratigraphic scheme of the late Miocene and early Pliocene of southern South America.
What a pandemic can say about human–environment relationship
Authors: Pettini Greta , Mazzocco Ketti
Published: June 2021

In 2020, the new coronavirus disease has seen many countries adopt mitigation activities to interrupt human‐to‐human transmission, radically changing daily life habits with secondary effects on the environment. The aim of this article is to comment on these events from a systemic point of view, referring to systems theories and the non‐linear causal relation between human behaviour and the environment. As Bateson stated, linear thinking has led human beings to exploit the environment, causing an ecological crisis and disequilibrium within the system, because the mutual interrelationship and homeostasis mechanisms between humans and their environment were ignored. Taking into account the pandemic and its effects, the new coronavirus provides an opportunity to see otherwise invisible or obscured relational phenomena, such as the mutual relationship between humans and their environment.
Global Well-Posedness of the Ocean Primitive Equations with Nonlinear Thermodynamics
Authors: Korn Peter
Published: June 2021

We consider the hydrostatic Boussinesq equations of global ocean dynamics, also known as the “primitive equations”, coupled to advection–diffusion equations for temperature and salt. The system of equations is closed by an equation of state that expresses density as a function of temperature, salinity and pressure. The equation of state TEOS-10, the official description of seawater and ice properties in marine science of the Intergovernmental Oceanographic Commission, is the most accurate equations of state with respect to ocean observation and rests on the firm theoretical foundation of the Gibbs formalism of thermodynamics. We study several specifications of the TEOS-10 equation of state that comply with the assumption underlying the primitive equations. These equations of state take the form of high-order polynomials or rational functions of temperature, salinity and pressure. The ocean primitive equations with a nonlinear equation of state describe richer dynamical phenomena than the system with a linear equation of state. We prove well-posedness for the ocean primitive equations with nonlinear thermodynamics in the Sobolev space $${{\mathcal {H}}^{1}}$$

H

1

. The proof rests upon the fundamental work of Cao and Titi (Ann. Math. 166:245–267, 2007) and also on the results of Kukavica and Ziane (Nonlinearity 20:2739–2753, 2007). Alternative and older nonlinear equations of state are also considered. Our results narrow the gap between the mathematical analysis of the ocean primitive equations and the equations underlying numerical ocean models used in ocean and climate science.
Prozesse der Emotionsregulierung in psychoanalytischen Langzeitpsychotherapien
Authors: Bänninger-Huber Eva
Published: June 2021

Das Projekt verfolgt das Ziel, das affektive Regulierungsgeschehen in psychotherapeutischen Interaktionen anhand von Videoaufnahmen mikroanalytisch zu beschreiben und mit einem produktiven therapeutischen Prozess in Beziehung zu setzen. Analysiert werden mimische Verhaltensweisen, die mit dem Facial Action Coding System (FACS) objektiv erfasst werden. Im Fokus des Beitrags stehen die sogenannten Prototypischen Affektiven Mikrosequenzen (PAMS). PAMs sind durch Lächeln und Lachen gekennzeichnet und dienen dazu, Störungen in der Affektregulierung mit Hilfe des Gegenübers auszuregulieren. Sie spielen in der therapeutischen Beziehung eine bedeutsame Rolle bei der Aufrechterhaltung einer Balance zwischen Beziehungssicherheit und Konfliktspannung. Unsere Analysen sollen dabei helfen, die Funktionen dieser weitgehend unbewussten Prozesse besser zu verstehen und für den therapeutischen Alltag nutzbar zu machen.
Distribution of clock correction and ephemeris parameters in broadcast navigation messages
Authors: Lapin Ivan , Samson Jaron , Wallner Stefan , Lopez Carlos , Mabilleau Mikael
Published: June 2021

The distribution of clock correction and ephemeris (CCE) parameters in navigation messages broadcast by operational satellite vehicles (SVs) of the Global Navigation Satellite System (GNSS) is studied. For this purpose, two evaluation metrics are proposed, namely atypical navigation message structures and time to complete CCE sets (TTCS). The evaluation metrics are used to analyze three and a half years of operational Galileo F/NAV and GPS LNAV messages. The study considers arbitrary and healthy-only signal-in-space (SIS) health statuses. The frequently used receiver independent exchange format (RINEX) navigation files are shown to not provide sufficient information to determine the CCE parameters transmitted at every time instance. Due to the identified limitations, binary navigation data collected by a worldwide network of monitoring stations are used for the analysis. During operations, the maximum of the TTCS metric is shown to be impacted by the issue of data (IOD) update periods and structures with mismatched IOD parameters, potentially introducing an additional delay to the time to first fix (TTFF). The message timing requirements of dual-frequency multi-constellation (DFMC) satellite-based augmentation system (SBAS) are shown to be in line with the minimum times needed to obtain multiple complete Galileo F/NAV and GPS LNAV CCE sets.
On the reliability of the equivalent frame models: the case study of the permanently monitored Pizzoli’s town hall
Authors: Degli Abbati Stefania , Morandi Paolo , Cattari Serena , Spacone Enrico
Published: June 2021

This paper presents the comparison of the results of modal and nonlinear analyses carried out on a 2-story masonry building with rigid diaphragms, inspired by the Pizzoli’s town hall (AQ, Italy). The case study is one of the Benchmark Structures (labeled BS6) in the “URM nonlinear modelling–Benchmark project” funded by the Italian Department of Civil Protection (DPC) within the framework of the ReLUIS projects. The building has been instrumented since 2009 with a permanent monitoring system by the Osservatorio Sismico delle Strutture (OSS) of the DPC and was hit by the 2016/2017 Central Italy earthquake sequence. In the research first phase, modal and nonlinear static analyses were carried out in a blind prediction, without any preliminary calibration of the models, but referring only to commonly made assumptions on materials and modelling. Five computer programs based on the Equivalent Frame Model (EFM) approach were used. Four different structural configurations were considered: with weak spandrels (A), with tie rods coupled to spandrels (B), with RC ring beams coupled to spandrels (C) and with “shear type” idealization (D). In the research second phase, two of the developed EFMs were calibrated in the elastic range using the results of available Ambient Vibration Tests (AVTs). The models were then validated in the nonlinear range by simulating the dynamic response of the structure recorded during the mainshocks of the 2016/2017 Central Italy earthquake. Recorded and numerical results were compared at both the global and local scale.
Co-expression of transcription factor AP-2beta (TFAP2B) and GATA3 in human mammary epithelial cells with intense, apicobasal immunoreactivity for CK8/18
Authors: Raap M. , Gierendt L. , Werlein C. , Kuehnle E. , Kreipe H. H. , Christgen M.
Published: June 2021

AP-2β is a new mammary epithelial differentiation marker and its expression is preferentially retained and enhanced in lobular carcinoma in situ and invasive lobular breast cancer. In normal breast epithelium AP-2β is expressed in a scattered subpopulation of luminal cells. So far, these cells have not been further characterized. Co-expression of AP-2β protein and luminal epithelium markers (GATA3, CK8/18), hormone receptors [estrogen receptor (ER), androgen receptor (AR)] and candidate stem cells markers (CK5/14, CD44) were assessed by double-immunofluorescence staining in normal mammary gland epithelium. The subpopulation of AP-2β-positive mammary epithelial cells showed an almost complete, superimposable co-expression with GATA3 and a peculiar intense, ring-like appearing immunoreactivity for CK8/18. Confocal immunofluorescence microscopy revealed an apicobasal staining for CK8/18 in AP-2β-positive cells, which was not seen in in AP-2β-negative cells. Furthermore, AP-2β-positive displayed a partial co-expression with ER and AR, but lacked expression of candidate stem cell markers CK5/14 and CD44. In summary, AP-2β is a new luminal mammary epithelial differentiation marker, which is expressed in the GATA3-positive subpopulation of luminal epithelial cells. These AP-2β-positive/GATA3-positive cells also show a peculiar CK8/18-expression which may indicate a previously unknown functionally specialized mammary epithelial cell population.
Design and regulation of balancing power auctions: an integrated market model approach
Authors: Ehrhart Karl-Martin , Ocker Fabian
Published: June 2021

We present an integrated market model which considers the dependencies between the wholesale market and the highly regulated balancing power markets. This fosters the understanding of the mechanisms of these markets and, thus, allows the evaluation of the designs of these markets and their interplay. In contrast to existing literature, in our model the prices on the different markets are interdependent and endogenously determined, which also applies to the switch from inframarginal suppliers to extramarginal suppliers. Linked to this, the implementation of a specific assignment of the suppliers to the different markets is according to their production costs and their ability to provide balancing power. We prove the existence of a market equilibrium, analyze its outcome and contrast this with German market data. Based on this model, we assess design changes, partly stipulated by recent European regulation. This includes uniform pricing as a common settlement rule (effect: no truthful bidding in general), standardized prequalification criteria (promising measure for cost reduction), market flexibilization via “free energy bids” (no increased competition) and the alternative score “mixed-price rule” (no effect on the equilibrium).
Polycyclic aromatic hydrocarbons (PAHs), arsenic, chromium and lead in warty crab (Eriphia verrucosa): occurrence and risk assessment
Authors: Lambiase Sara , Ariano Andrea , Serpe Francesco Paolo , Scivicco Marcello , Velotto Salvatore , Esposito Mauro , Severino Lorella
Published: June 2021

This study assesses the PAH and heavy metal levels in muscle of warty crabs (Eriphia verrucosa), from the northern coast of the Campania region improving the data on toxic contaminants in this crustacean. The results showed a minimal PAH contamination; the mean concentrations were as follows: 0.2, 1.6 and 1.7 μg kg-1 wet weight (ww) for BaP, PAH4 and PAH6, respectively. Regarding the levels of the two PAHs not included in the European regulations, the BkF mean concentration was 0.1 μg kg-1 ww, while DahA was detected only in 10.7% of samples. Pb and Cr were also detected at low levels with mean values of 0.068 and 0.468 mg kg-1 ww, respectively; instead, high As levels, with a mean value of 5.021 mg kg-1 ww, were found. Considering the EWIs and the ILCRs calculated in this study, the PAH, Pb and Cr contamination levels found in the edible part of the crabs resulted safe for human consumption. Contrariwise, the ILCR calculated for the As exceeded the acceptable level of cancer risk, although the calculation did not refer to the inorganic form which is the only one recognized as carcinogenic. Hence, this study shows that warty crabs can accumulate environmental contaminants in their muscle tissue representing an important route of exposure to these toxics for the local population that regularly consumes them. This finding highlights the importance of monitoring the presence of these pollutants in crabs and in general in all fish and seafood in order to ensure food safety for consumers.
Characterization of Hoek–Brown constant mi of quasi-isotropic intact rock using rigidity index approach
Authors: Davarpanah Seyed Morteza , Sharghi Mohammad , Vásárhelyi Balázs , Török Ákos
Published: June 2021

An accurate determination of Hoek–Brown constant mi is of great significance in the estimation of the failure criteria of brittle rock materials. So far, different approaches such as rigidity index method (R-index), uniaxial compressive strength-based method, and tensile strength-based method, and the combination of these two methods (combination based method) have been proposed to calculate the value of mi. This paper aims to thoroughly review the previously existing methods to calculate the value of mi and make comparison between the obtain results to propose the new material constants that provide the best fit with the experimental data. In order to fulfill this goal, a large number of data for different quasi-isotropic intact rock types from the literature were collected and statistically analyzed. Additionally, based on rock types, new material constants are introduced for igneous, sedimentary, and metamorphic rocks. The obtained results proves that for different rock groups (igneous, sedimentary, and metamorphic rocks), R-index method provides the best fit with the experimental data among the others, and it is also independent of rock type. Interestingly enough, there is significant differences in the predicted mi values using different methods, which is more probably due to the quantity and quality of data used in the statistical analysis.
Unterrichtsqualität und intrinsische Lesemotivation im Kontext der Bund-Länder-Initiative „Bildung durch Sprache und Schrift“ (BiSS)
Authors: Ohle-Peters Annika , Igler Jennifer , Schlitter Theresa , Teerling Annika , Köller Olaf , McElvany Nele
Published: June 2021

Lesekompetenz gilt als fächerübergreifende Schlüsselkompetenz für Bildungserfolg und ist damit ein zentrales Ziel des Grundschulunterrichts. Vor diesem Hintergrund zielte die Bund-Länder-Initiative „Bildung durch Sprache und Schrift“ unter anderem auf die Förderung lesebezogener Kompetenzen im Leseunterricht der Grundschule ab. Der intrinsischen Lesemotivation kommt aufgrund ihres eigenständigen Wertes und wegen ihrer Zusammenhänge mit der Lesekompetenz eine große Bedeutung zu. Der vorliegende Beitrag untersucht a) Zusammenhänge zwischen schulischer BiSS-Beteiligung und der Entwicklung der Qualität des Leseunterrichts in einem quasi-experimentellen Längsschnittdesign mitN = 1032 Schülerinnen und Schülern der vierten Klassenstufe und b) Zusammenhänge von Unterrichtsqualität und der Entwicklung intrinsischer Lesemotivation. Es wurden Mehrebenenstrukturgleichungsmodelle spezifiziert und analysiert, die einen kleinen positiven Effekt schulischer BiSS-Beteiligung auf die Differenzierung im Leseunterricht zeigten. Außerdem erwiesen sich Differenzierung, Störungen im Unterricht und Merkmale des unterstützenden Unterrichtsklimas als prädiktiv für intrinsische Lesemotivation auf Individualebene.
Severe intraoperative bleeding predicts the risk of perioperative blood transfusion after robot-assisted radical prostatectomy
Authors: Porcaro Antonio Benito , Rizzetto Riccardo , Amigoni Nelia , Tafuri Alessandro , Shakir Aliasger , Tiso Leone , Cerrato Clara , Antoniolli Stefano Zecchini , Lacola Vincenzo , Gozzo Alessandra , Odorizzi Katia , Orlando Rossella , Di Filippo Giacomo , Brunelli Matteo , Migliorini Filippo , De Marco Vincenzo , Artibani Walter , Cerruto Maria Angela , Antonelli Alessandro
Published: June 2021

To evaluate potential factors associated with the risk of perioperative blood transfusion (PBT) with implications on length of hospital stay (LOHS) and major post-operative complications in patients who underwent robot-assisted radical prostatectomy (RARP) as a primary treatment for prostate cancer (PCa). In a period ranging from January 2013 to August 2019, 980 consecutive patients who underwent RARP were retrospectively evaluated. Clinical factors such as intraoperative blood loss were evaluated. The association of factors with the risk of PBT was investigated by statistical methods. Overall, PBT was necessary in 39 patients (4%) in whom four were intraoperatively. Positive surgical margins, operating time and intraoperative blood loss were associated with perioperative blood transfusion on univariate analysis. On multivariate analysis, the risk of PBT was predicted by intraoperative blood loss (odds ratio, OR 1.002; 95% CI 1.001–1.002; p < 0.0001), which was associated with prolonged operating time and elevated body mass index (BMI). PBT was associated with delayed LOHS and Clavien–Dindo complications > 2. In patients undergoing RARP as a primary treatment for PCa, the risk of PBT represented a rare event that was predicted by severe intraoperative bleeding, which was associated with increased BMI as well as with prolonged operating time. In patients who received a PBT, prolonged LOHS as well as an elevated risk of major Clavien–Dindo complications were seen.
Post San Antonio update—my top three abstracts!
Authors: Suppan Christoph
Published: June 2021

Recent findings support the role of alpelisib in advanced HR-positive breast cancer harboring a PIK3CA mutation. A retrospective biomarker analysis on the intrinsic subtypes of HR-positive breast cancer reveals a subgroup that will not benefit under the addition of a CDK 4/6 inhibitor treatment. The detection of circulating tumor cells before start and during tumor treatment is associated with worse outcome in metastatic breast cancer patients.
Congestive heart failure and comorbidity as determinants of colorectal cancer perioperative outcomes
Authors: Basso Cristina , Gennaro Nicola , Dotto Matilde , Ferroni Eliana , Noale Marianna , Avossa Francesco , Schievano Elena , Aceto Paola , Tommasino Concezione , Crucitti Antonio , Incalzi Raffaele Antonelli , Volpato Stefano , Petrini Flavia , Carron Michele , Pace Maria Caterina , Bettelli Gabriella , Chiumiento Fernando , Corcione Antonio , Montorsi Marco , Trabucchi Marco , Maggi Stefania , Corti Maria Chiara
Published: June 2021

There has been an increase in surgical interventions in frailer elderly with concomitant chronic diseases. The purpose of this paper was to evaluate the impact of aging and comorbidities on outcomes in patients who underwent surgery for the treatment of colorectal cancer (CRC) in Veneto Region (Northeastern Italy). This is a retrospective cohort study in patients ≥ 40 years who underwent elective or urgent CRC surgical resection between January 2013 and December 2015. Independent variables included: age, sex, and comorbidities. We analyzed variables associated with the surgical procedure, such as stoma creation, hospitalization during the year before the index surgery, the surgical approach used, the American Society of Anesthesiologists (ASA) score, and the Charlson Comorbidity Index score. Eight thousand four hundred and forty-seven patients with CRC underwent surgical resection. Patient age affected both pre- and post-resection LOS as well as the overall survival (OS); however, it did not affect the 30-day readmission and reoperation rates. Multivariate analysis showed that age represented a risk factor for longer preoperative and postoperative LOS as well as for 30-day and 365-day mortality, but it was not associated with an increased risk of 30-day reoperation and 30-day readmission. Chronic Heart Failure increased the 30-day mortality risk by four times, the preoperative LOS by 51%, and the postoperative LOS by 33%. Chronic renal failure was associated with a 74% higher 30-day readmission rate. Advanced age and comorbidities require a careful preoperative evaluation and appropriate perioperative management to improve surgical outcomes in older patients undergoing elective or urgent CRC resection.
A River Flood and Earthquake Risk Assessment of Railway Assets along the Belt and Road
Authors: Wang Qianzhi , Liu Kai , Wang Ming , Koks Elco E.
Published: June 2021

Mitigating the disaster risk of transportation infrastructure networks along the Belt and Road is crucial to realizing the area’s high trade potential in the future. This study assessed the exposure and risk of existing and planned railway assets to river flooding and earthquakes. We found that about 9.3% of these railway assets are exposed to a one in 100 year flood event, and 22.3% are exposed to a one in 475 year earthquake event. The combined flood and earthquake risk of physical damage to railway assets, expressed by expected annual damage (EAD), is estimated at USD 1438 (between 966 and 2026) million. Floods contribute the majority of the risk (96%). China has the highest EAD for both floods and earthquakes (between USD 240 and 525 million in total). Laos and Cambodia are the countries with the highest EAD per km from flooding (USD 66,125–112,154 and USD 31,954–56,844 per km, respectively), while Italy and Myanmar have the highest EAD per km from earthquakes (USD 1000–3057 and USD 893–3019 per km, respectively). For the newly built and planned projects along the Belt and Road, the EAD is estimated at USD 271 (between 205 and 357) million. The China–Indochina Peninsula Economic Corridor and China–Pakistan Economic Corridor have the highest absolute EAD and EAD per km, with EADs reaching USD 95 and USD 67 million, and USD 18 and USD 17 thousand per km, on average, respectively. For railway segments with high risks, we found that if the required adaptation cost within 20 years to realize a 10% increase of the railway quality is below 8.4% of the replacement cost, the benefits are positive.
The system, the resident, and the preceptor: a curricular approach to continuity of care training
Authors: Merbaum Allyson , Kulasegaram Kulamakan , Stoller Rebecca , Fernando Oshan , Freeman Risa
Published: June 2021

Background Continuity of care (CoC) is integral to the practice of comprehensive primary care, yet research in the area of CoC training in residency programs is limited. In light of distributed medical education and evolving accreditation standards, a rigorous understanding of the context and enablers contributing to CoC education must be considered in the design and delivery of residency training programs.

Approach At our preceptor-based community academic site, we developed a system—resident—preceptor (SRP) framework to explore factors that influence a resident’s perception regarding CoC, and established variables in each area to enhance learning. We then implemented a two-year educational SRP intervention (SRPI) to one cohort of residents and their preceptors to integrate critical education factors and align teaching of continuity of care within curricular goals.

Evaluation Evaluation of the intervention was based on resident interviews and faculty focus groups, and a qualitative phenomenological approach was used to analyze the data. While some factors identified are inherent to family medicine, the opportunity for reflection is a unique component to inculcate CoC learning.

Reflection The SRP innovation provides a unique framework to facilitate residents’ understanding and development of CoC competency. Our model can be applied to all residency programs, including traditional academic sites as well as distributed training sites, to enhance CoC education.
Association between hyperkalemia, RAASi non-adherence and outcomes in chronic kidney disease
Authors: Santoro Antonio , Perrone Valentina , Giacomini Elisa , Sangiorgi Diego , Alessandrini Davide , Degli Esposti Luca
Published: June 2021

Background

Hyperkalemia is relatively frequent in CKD patients treated with renin-angiotensin-aldosterone-system inhibitors (RAASi).

Aim

The aim of the present study was to estimate the increased risk of cardiovascular events and mortality due to sub-optimal adherence to RAASi in CKD patients with hyperkalemia.

Methods

An observational retrospective cohort study was conducted, based on administrative and laboratory databases of five Local Health Units. Adult patients discharged from the hospital with a diagnosis of CKD, who were prescribed RAASi between January 2010 and December 2017, were included. We evaluated the appearance of documented episodes of hyperkalemia, RAASi therapy adherence and the effects of these two variables on cardiovascular events, death and dialysis inception for study patients.

Results

Of the 9241 selected patients, 4451 met all the criteria for study inclusion. Among them, 1071 had at least one documented episode of hyperkalemia, while 3380 did not. After propensity score matching based on several variables we obtained 2 groups of patients. The appearance of hyperkalemia caused treatment discontinuation in 21.8% of patients previously on RAASi therapy, and sub-optimal adherence (proportion of days covered  < 80%) in 33.6% of them. Non-adherence to RAASi therapy among hyperkalemia patients was associated with a higher risk of cardiovascular events (hazard ratio [HR] 1.45, confidence interval [CI] 1.02–2.08; p < 0.05). Moreover, in non-adherent hyperkalemia patients, the risk of death increased by 126% (HR 2.26, CI 1.62–3.15; p < 0.001) compared with adherent patients.

Conclusions

In a large cohort of CKD patients treated with RAASi, we observed that following hyperkalemia onset, non-adherence to RAASi medication can result in an increased risk of cardiovascular events and death.

Graphical abstract
Die Soziale Marktwirtschaft nach der Corona-Krise: Fit für den Systemwettbewerb im 21. Jahrhundert
Authors: Schmidt Christoph M.
Published: June 2021

Die Soziale Marktwirtschaft ist auch in Zeiten des verschärften Systemwettbewerbs mit den USA und China die geeignete Wirtschafts- und Gesellschaftsordnung für Deutschland und Europa, um die Volkswirtschaft auf einen nachhaltigen Wachstumspfad zu führen. Nur ein wirtschaftlich erfolgreiches Europa wird erfolgreich dabei mitwirken, das 21. Jahrhundert auf Basis der eigenen Werte als eine Ära der weltumspannenden materiellen Prosperität und ökologischen Nachhaltigkeit zu gestalten. Daher gilt es vor allem, die europäische Klimapolitik marktwirtschaftlich auszugestalten und die eigene Regeltreue und Vorbildlichkeit bei der Umsetzung globaler Vertragswerke mit hoher Bereitschaft zum Finanz- und Technologietransfer zu verbinden.
Elucidation of Regional Mechanical Properties of Brain Tissues Based on Cell Density
Authors: Zhang Chi , Qian Long , Zhao Hongwei
Published: June 2021

Research on the mechanical properties of brain tissue has received extensive attention. However, most of the current studies have been conducted at the phenomenological level. In this study, the indentation method was used to explore the difference in local mechanical properties among different regions of the porcine cerebral cortex. Further, hematoxylin-eosin and immunofluorescence staining methods were used to determine the correlation between the cellular density at different test points and mechanical properties of the porcine cerebral cortex. The frontal lobe exhibited the strongest viscosity. The temporal lobe displayed the lowest sensitivity to changes in the indentation speed, and the occipital lobe exhibited the highest shear modulus. Additionally, the shear modulus of different areas of the cerebral cortex was negatively correlated with the total number of local cells per unit area and positively correlated with the number of neuronal cell bodies per unit area. Exploration of the mechanical properties of the local brain tissue can provide basic data for the establishment of a finite element model of the brain and mechanical referential information for the implantation position of brain chips.