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Given that not all suggestions can be implemented, understanding how supervisors can turn down employee voiced suggestions while not discouraging employees voicing in the future is critical for theoretical and practical reasons. Supervisors may use humour when not endorsing employees' suggestions as they attempt to ease tension by injecting something lighthearted, but doing so, we argue, is not uniformly beneficial. Hence, we conducted a preregistered study that tests how supervisors' use of humour when turning down an employee's voiced suggestion affects voice resilience. Utilizing signaling theory, we theorize supervisors' use of humour when turning down voice strengthens voice safety but weakens voice impact perceptions. Indirectly, humour therefore may constitute a mixed blessing for voice resilience (voice behaviour after voice non‐endorsement). Additionally, we hypothesized that the positive link between humour and voice safety and the negative link between humour and voice impact are moderated by supervisor–employee relationship quality (leader–member exchange (LMX)). We tested these predictions in a time‐lagged study of 343 employees whose voice was recently turned down. Humour indeed increased voice resilience via voice safety; against expectations, humour positively related to voice impact (via it, resilience). LMX is significantly moderated. However, unexpectedly, humour helped voice safety, impact and the resilience of low LMX employees. [ABSTRACT FROM AUTHOR]

Aims: Type 1 diabetes mellitus (T1DM) is characterised by insulin deficiency. Due to perceived physical activity (PA)‐related hypoglycaemia, a minority of people with T1DM exercise regularly. However, the relationship between T1DM and PA remains poorly understood. Our aim was to summarise the existing literature on the effects of PA on short‐term glucose control (glycated haemoglobin or time in range) in people with T1DM. Methods: We searched seven electronic databases (PubMed, Embase, Cochrane library, Cinahl, SPORTDiscus, PEDro and Web Of Science) and two sources of the grey literature (ClinicalTrials.gov and ICTRP). All reviews were screened via title/abstract and full text by two independent reviewers (LE and HT), conflicts were solved by a third independent reviewer (DDC). We excluded animal studies, case reports, non‐English articles, qualitative studies, conference abstracts and articles without full‐text access. A meta‐analysis using random effects model was performed to study the effect of PA on haemoglobin A1c (HbA1c) levels in people with T1DM. Results: We obtained 19,201 unique references across nine different electronic databases. After screening and snowballing, 68 articles were found investigating the effect of PA on glycaemic control in people with T1DM. Overall, HbA1c levels in the PA group (mean difference = 0.29% (0.20%–0.39%)), were lower compared with the control group. Conclusion: An overall small beneficial effect of PA on glycaemic control in people with T1DM was found. Caution is advised when interpreting the results of this meta‐analysis, given variations in study type, duration, frequency and intensity of physical activity across included studies. [ABSTRACT FROM AUTHOR]

Digital flourishing refers to the positive perceptions of digital communication use in five dimensions: connectedness, positive social comparison, authentic self‐presentation, civil participation, and self‐control. This three‐wave panel study among 1081 Slovenian adolescents (Mage = 15.34 years, 53.8% boys, 80.7% ethnic majority) explored the trajectories of their digital flourishing dimensions over 1 year (2021–2022). Latent class growth analysis identified two classes. Adolescents in the first class reported high levels of digital flourishing, which remained stable over time, whereas those in the second class reported low levels of digital flourishing with decreased self‐control over time. Autonomy‐supportive restrictive, autonomy‐supportive active, and controlling active parental mediation styles, together with high parental digital skills, predicted adolescents' belongingness to the (more digitally flourishing) first class. [ABSTRACT FROM AUTHOR]

Background: The noninflammatory immunoglobulin G4 (IgG4) is linked to tolerance and is unique to humans. Although poorly understood, prolonged antigenic stimulation and IL‐4‐signaling along the T helper 2‐axis may be instrumental in IgG4 class switching. Recently, repeated SARS‐CoV‐2 mRNA vaccination has been linked to IgG4 skewing. Although widely used immunosuppressive drugs have been shown to only moderately affect humoral responses to SARS‐CoV‐2 mRNA vaccination, the effect on IgG4 switching has not been investigated. Methods: Here we study the impact of such immunosuppressive drugs, including the IL‐4 receptor‐blocking antibody dupilumab, on IgG4 skewing upon repeated SARS‐CoV‐2 mRNA vaccination. Receptor‐binding domain (RBD) specific antibody responses were longitudinally measured in 600 individuals, including patients with immune‐mediated inflammatory diseases treated with a TNF inhibitor (TNFi) and/or methotrexate (MTX), dupilumab, and healthy/untreated controls, after repeated mRNA vaccination. Results: We observed a substantial increase in the proportion of RBD‐specific IgG4 antibodies (median 21%) in healthy/untreated controls after third vaccination. This IgG4 skewing was profoundly reduced in dupilumab‐treated patients (<1%). Unexpectedly, an equally strong suppression of IgG4 skewing was observed in TNFi‐treated patients (<1%), whereas MTX caused a modest reduction (7%). RBD‐specific total IgG levels were hardly affected by these immunosuppressive drugs. Minimal skewing was observed, when primary vaccination was adenoviral vector‐based. Conclusions: Our results imply a critical role for IL‐4/IL‐13 as well as TNF in vivo IgG4 class switching. These novel findings advance our understanding of IgG4 class switch dynamics, and may benefit humoral tolerance induction strategies, treatment of IgG4 pathologies and mRNA vaccine optimization. [ABSTRACT FROM AUTHOR]

Specialized pro‐resolving lipid mediators (SPMs) are known for their anti‐inflammatory and pro‐resolving actions. The aim of the present study was to find new functions of the SPM resolvin D1n‐3 DPA (RvD1n‐3 DPA) on oral epithelial cells. As a starting point, we used a dataset obtained by RNA high‐throughput sequencing of oral epithelial cells exposed to TNF‐α and RvD1n‐3 DPA versus TNF‐α alone. GOrilla enrichment analysis showed that the actin cytoskeleton was significantly overrepresented after adjustment for multiple hypothesis testing. As actin, amongst others, is closely related to cell migration, we then explored whether RvD1n‐3 DPA can modulate oral epithelial cell migration. To this end, we used an in vitro cell migration model, including TNF‐α treatment, to mimic an inflammatory cell state. The analysis revealed that RvD1n‐3 DPA increased oral epithelial cell migration in the presence but not in the absence of TNF‐α. Addition of RvD1n‐3 DPA also induced F actin accumulation around the cell nucleus, indicating that RvD1n‐3 DPA potentially can mediate processes of intracellular transport. This indicates that this lipid mediator may be a promising therapeutic candidate in oral mucosal wound healing. [ABSTRACT FROM AUTHOR]

The global climate change negatively affects the photovoltaic performance of traditional solar cell technologies. This article investigates the potential of organic photovoltaics (OPV) for high‐temperature environments, ranging from urban hot summers (30—40 °C) and desert regions (65 °C) up to (aero) space conditions (130 °C), the thermal window in which OPV can operate. The approach is based on a combination of experiments and simulations up to 180 °C, moving significantly beyond the conventional temperature ranges reported in the literature. New 2H‐benzo[d][1,2,3]triazole‐5,6‐dicarboxylic imide‐based copolymers with decomposition onset temperatures above 340 °C are used for this study, in combination with non‐fullerene acceptors. Contrary to their inorganic counterparts, OPV devices show a positive temperature coefficient up to ≈90 °C. At temperatures of 150 °C, they are still operational, retaining their room temperature efficiency. Complementary simulations are performed using an in‐house developed software package that numerically solves the drift‐diffusion equations to understand the general trends in the obtained current–voltage characteristics and the materials' intrinsic behavior as a function of temperature. The presented methodology of combined high‐temperature experiments and simulations can be further applied to investigate the thermal window of operation for other OPV material systems, opening novel high‐temperature application routes. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the incidence, diagnostic management strategies and clinical outcomes of women with spontaneous haemoperitoneum in pregnancy (SHiP) and reassess the definition of SHiP. Design: A population‐based cohort study using the Netherlands Obstetric Surveillance System (NethOSS). Setting: Nationwide, the Netherlands. Population: All pregnant women between April 2016 and April 2018. Methods: This is a case study of SHiP using the monthly registry reports of NethOSS. Complete anonymised case files were obtained. A newly introduced online Delphi audit system (DAS) was used to evaluate each case, to make recommendations on improving the management of SHiP and to propose a new definition of SHiP. Main outcome measures: Incidence and outcomes, lessons learned about clinical management and the critical appraisal of the current definition of SHiP. Results: In total, 24 cases were reported. After a Delphi procedure, 14 cases were classified as SHiP. The nationwide incidence was 4.9 per 100 000 births. Endometriosis and conceiving after artificial reproductive techniques were identified as risk factors. No maternal and three perinatal deaths occurred. Based on the DAS, adequate imaging of free intra‐abdominal fluid, and identifying and treating women with signs of hypovolemic shock could improve the early detection and management of SHiP. A revised definition of SHiP was proposed, excluding the need for surgical or radiological intervention. Conclusions: SHiP is a rare and easily misdiagnosed condition that is associated with high perinatal mortality. To improve care, better awareness among healthcare workers is needed. The DAS is a sufficient tool to audit maternal morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC‐specific survival (BCSS) compared to non‐carriers. Aim: To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Methods: Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow‐up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi‐state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. Results: There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55–0.78)]. No association was observed with radiotherapy. Results from the multi‐state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non‐carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09–1.56)]. Conclusion: Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk. [ABSTRACT FROM AUTHOR]

Bullous pemphigoid (BP) is characterized by deposition of immunoglobulins and complement along the epidermal basement membrane (BM). In humans, there is a lack of functional studies targeting the complement system (CS). This study investigates activation of all complement pathways in BP skin biopsies. Moreover, pharmacological inhibition at different levels of the CS was investigated using anti‐complement compounds in a complement fixation BP assay. In this retrospective study, 21 frozen biopsies from BP patients were stained by direct immunofluorescence for C1q, MBL, ficolin‐2, C4d, properdin, C3c and C5b‐9. Sera from 10 patients were analysed in a complement fixation assay in the presence of C1 inhibitor, anti‐factor B monoclonal antibody (mAb), anti‐C3 mAb and anti‐C5 mAb and compared with dexamethasone. The two readouts were the quantity of complement deposited along the BM and the release of sC5b‐9 in the supernatant. Our results show classical and alternative complement pathway activation in BP skin biopsies, but could not demonstrate significant lectin pathway activation. In contrast to dexamethasone, complement deposition along the BM could be selectively inhibited by anti‐C1 and anti‐ factor B. More downstream, selective intervention at the level of C3 and C5 could effectively reduce complement deposition along the BM and the release of sC5b‐9 in the supernatant. This study shows that selective intervention in either the classical, alternative or terminal pathway prevented deposition of complement along the BM in an in vitro BP model. The results of our study greatly encourage the clinical development of complement inhibitors for the treatment of BP. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma of the tongue (OTSCC) is the most common malignancy among oral squamous cell carcinomas and is frequently associated with an unfavorable prognosis. Local spread and distant metastasis are important causes of poor prognosis in OTSCC. Cortactin amplification and overexpression, a common molecular alteration in oral squamous cell carcinomas, have been linked to invasion and metastasis of tumor cells. However, the intra‐tumor expression pattern and prognostic significance of cortactin in human papillomavirus (HPV) negative OTSCC is not fully investigated. Immunohistochemical analysis using tissue microarray consisting of formalin‐fixed and paraffin‐embedded HPV negative OTSCC (n = 123) specimens showed overexpression of cortactin at tissue cores from invading fronts as compared to the corresponding center cores. High overall cortactin expression was found to be associated with advanced (larger) tumor size and the occurrence of distance metastasis. Kaplan‐Meier survival analysis showed that patients with high overall cortactin expression were associated with reduced 5‐year survival. Multivariate Cox regression analysis identified high cortactin expression to be an independent prognostic factor in OTSCC. Additionally, siRNA‐mediated silencing of cortactin was found to suppress the proliferative and invasive abilities of OTSCC cells in an organotypic co‐culture model. Overexpression of cortactin is a promising prognostic marker in HPV‐negative OTSCC. [ABSTRACT FROM AUTHOR]

Private standards play an increasingly important governance role, yet their effects on state‐led policymaking remain understudied. We examine how the operation of private agricultural standards influences multilateral pesticide governance with a particular focus on the listing of substances under the Rotterdam Convention on the Prior Informed Consent Procedure for Certain Hazardous Chemicals and Pesticides in International Trade, a treaty‐based information‐sharing mechanism that allows countries to refuse hazardous chemical imports. We find that private agricultural standard‐setting bodies use the Rotterdam Convention's pesticide list to develop their own lists of banned substances. This alters the Rotterdam Convention's intended role, impeding efforts to add substances to the treaty, as attempts by private actors to impose stricter governance than state actors can undermine the potential for international state‐based governance to become more stringent. We characterize this as a "confounding interaction" whereby institutional linkages between actions by public and private actors with broadly aligned goals results in unexpected negative consequences for governance. [ABSTRACT FROM AUTHOR]

In 2020, Australia's successful COVID‐19 public health restrictions comprised a national "initial lockdown" (March–May) and "ongoing lockdown" (July–November) for metropolitan Victorian residents only. We evaluated associations between ongoing lockdown and family finances and mental health. In the June and September 2020 Royal Children's Hospital National Child Health Polls, caregivers of children in Victoria and New South Wales (NSW) reported the following: job/income loss; material deprivation (inability to pay for essential items); income poverty; mental health (Kessler‐6); perceived impact on caregiver/child mental health; and caregiver/child coping. Data from caregivers (N = 1207/902) in June/September were analysed using difference‐in‐difference modelling (NSW provided the comparator). During Victoria's ongoing lockdown, job/income loss increased by 11% (95%CI: 3%–18%); Kessler‐6 poor mental health by 6% (95%CI: −0.3%–12%) and perceived negative mental health impacts by 14% for caregivers (95%CI: 6%–23%) and 12% for children (95%CI: 4%–20%). Female (vs. male) caregivers, metropolitan (vs. regional/rural) families, and families with elementary school‐aged children (vs. pre‐/high‐school) were the most affected. The ongoing lockdown was associated with negative experiences of mental health, employment and income, but not deprivation or poverty, likely because of government income supplements introduced early in the pandemic. Future lockdowns require planned responses to outbreaks and evidence‐informed financial and mental health supports. [ABSTRACT FROM AUTHOR]

Rifting and continental break-up are fundamental tectonic processes, the understanding of which is of prime importance. However, the vast temporal and spatial scales involved pose major limitations to researchers. Analog tectonic modeling represents a great means to mitigate these limitations, but studying the complex internal deformation of lithospheric-scale models remains a challenge. We therefore present a novel method for lithospheric-scale rifting models that are uniquely monitored in an X-ray CT scanner, which combined with digital image correlation (DIC) techniques, provides unparalleled insights into model deformation. Our first models illustrate how the degree of coupling between competent lithospheric layers, which are separated by a weak lower crustal layer, strongly impacts rift system development. Low coupling isolates the upper crust from the upper lithospheric mantle layer below, preventing an efficient transfer of deformation between both layers. By contrast, fast rifting increases coupling, so that deformation in the mantle is efficiently transferred to the upper crust, inducing either a symmetric or asymmetric (double) rift system. Furthermore, oblique divergence may lead to en echelon graben arrangements and delayed exhumation of the lower crustal layer. The successful application of our novel modeling approach, yielding these first-order insights, provides a clear incentive to continue running lithospheric-scale rifting models, and to apply advanced monitoring techniques to extract as much information from models as possible. There is indeed a broad range of opportunities for follow-up studies within (and beyond) the field of rift tectonics. [ABSTRACT FROM AUTHOR]

Background: Fetal growth restriction (FGR) is an obstetric complication associated with adverse perinatal outcomes. Doppler ultrasound can improve perinatal outcomes through monitoring at‐risk fetuses and helping time delivery. Aim: To investigate the prognostic value of different Doppler ultrasound measurements for adverse perinatal outcomes. Materials: Individual participant data. Methods: We performed a pooled analysis on individual participant data. We compared six prognostic models using multilevel logistic regression, where each subsequent model added a new variable to a base model that included maternal characteristics. Estimated fetal weight (EFW) and four Doppler ultrasound measurements were added in turn: umbilical artery pulsatility index (UA PI), middle cerebral artery pulsatility index (MCA PI), cerebroplacental ratio (CPR), and mean uterine artery pulsatility index (mUtA PI). The primary outcome was a composite adverse perinatal outcome, defined as perinatal mortality, emergency caesarean delivery for fetal distress, or neonatal admission. Discriminative ability was quantified with area under the curve (AUC). Results: Three data sets (N = 3284) were included. Overall, the model that included EFW and UA PI improved AUC from 0.650 (95% CI 0.624–0.676) to 0.673 (95% CI 0.646–0.700). Adding more ultrasound measurements did not improve further the discriminative ability. In subgroup analysis, the addition of EFW and UA PI improved AUC in both preterm (AUC from 0.711 to 0.795) and small for gestational age pregnancies (AUC from 0.729 to 0.770), but they did not improve the models in term delivery or normal growth subgroups. Conclusions: Umbilical artery pulsatility index added prognostic value for adverse perinatal outcomes to the already available information, but the combination of other Doppler ultrasound measurements (MCA PI, CPR or UtA PI) did not improve further prognostic performance. [ABSTRACT FROM AUTHOR]

Sensitization detected by ALEX®2 was consolidated according to allergen families when possible; for example, house dust mite allergen components Der p1, Der p 2, and Der p 5 were evaluated as one group. .001 ht 1 I Note i : ALEX®2 data of allergen-sensitized children were consolidated according to the major allergen families when possible and total IgE (cutoff IgE >=0.35 kUA/L). 1 TABLE Changes in ALEX®2 detected specific IgE in children sensitized for different allergens and allergen families before and after MV infection. In ALEX®2, total IgE was significantly decreased, but the only allergen-specific IgE antibodies to show a significant decrease over time were directed against grass pollen (Figures S3 and S4). [Extracted from the article]

Chronic inflammatory responses can inflict permanent damage to host tissues. Specialized pro‐resolving mediators downregulate inflammation but also can have other functions. The aim of this study was to examine whether oral epithelial cells express the receptors FPR2/ALX and DRV1/GPR32, which bind RvD1n‐3 DPA, a recently described pro‐resolving mediator derived from omega‐3 docosapentaenoic acid (DPA), and whether RvD1n‐3 DPA exposure induced significant responses in these cells. Gingival biopsies were stained using antibodies to FPR2/ALX and DRV1/GPR32. Expression of FPR2/ALX and DRV1/GPR32 was examined in primary oral epithelial cells by qRT‐PCR, flow cytometry, and immunofluorescence. The effect of RvD1n‐3 DPA on intracellular calcium mobilization and transcription of beta‐defensins 1 and 2, and cathelicidin was evaluated by qRT‐PCR. FPR2/ALX and DRV1/GPR32 were expressed by gingival keratinocytes in situ. In cultured oral epithelial cells, FPR2/ALX was detected on the cell surface, whereas FPR2/ALX and DRV1/GPR32 were detected intracellularly. Exposure to RvD1n‐3 DPA induced intracellular calcium mobilization, FPR2/ALX internalization, DRV1/GPR32 translocation to the nucleus, and significantly increased expression of genes coding for beta‐defensin 1, beta‐defensin 2, and cathelicidin. This shows that the signal constituted by RvD1n‐3 DPA is recognized by oral keratinocytes and that this can strengthen the antimicrobial and regulatory potential of the oral epithelium. [ABSTRACT FROM AUTHOR]

The lower parts of warm, thick continental crust can flow in a ductile fashion to accommodate thinning of the upper brittle crust during extension. Naturally occurring continental rifts with a rift‐axis parallel deformation gradient imply an underlying rotational component. In such settings, rift‐parallel crustal flow transports material perpendicular to the direction of rifting. We use analog experiments to investigate rotational rifting and coeval crustal flow. To test the effect of rift‐axis parallel flow on rift evolution, we use different gravitational loads resulting in a range of horizontal pressure gradient magnitudes which drive horizontal lower‐crustal flow. The use of (three dimensional) 3D Digital Volume Correlation techniques on X‐ray CT data combined with 3D Digital Image Correlation techniques applied to topographic stereo images provides detailed insights on the contemporaneous evolution of ductile flow patterns and brittle rift structures, respectively. Our results depict a complex flow field in the ductile lower crust during rotational rifting with: (a) extension‐parallel horizontal inward flow and vertical upward flow that compensates thinning of the brittle upper crustal layer; (b) rift‐axis parallel lateral flow, that compensates greater amounts of thinning further away from the rotation axis; and (c) different degrees of mechanical coupling between the brittle and viscous layers that change during rift propagation. Our analog experiments provide insights into ductile lower crustal flow patterns during rift evolution. The results emphasize the three dimensionality of rifting, which is an important effect that should be considered when estimating the amount of crustal extension from two dimensional (2D) cross sections. Plain Language Summary: Stretching of continental plates produces rifts, that are characterized by narrow fault zones in the brittle, upper parts of the Earth's crust and flow of rocks in the more ductile, lower parts of the crust. As rifts often propagate in one direction, the flow pattern in the lower crust can be complex and challenging to study and interpret. Here, we use laboratory experiments to investigate flow in propagating rifts. The application of X‐ray CT‐scanning allows us not only to visualize the model internal deformation, but also to quantify the deformation which provides detailed insights into the coeval evolution of ductile flow patterns and brittle rift structures. Our results document a complex 3D flow pattern within the lower crust with an important component along the rift axis, emphasizing the need to consider the evolution of rifts in 3D. Key Points: We use volumetric and surface image correlation techniques to depict coeval brittle rifting and ductile flow patterns in analog modelsRotational rifting promotes rift‐axis parallel lateral flow, causing outflow of lower crustal material away from the rotation axisPartial coupling of rift‐axis parallel displacements in the brittle and viscous domain is transient and dynamic over time [ABSTRACT FROM AUTHOR]

Krüppel‐like factor 4 (KLF4) is a zinc‐finger transcription factor involved in inflammation, cancer development, and progression. However, the relationship between KLF4, inflammation, and prognosis in oral cancer is not fully understood. KLF4 expression levels were examined in a multicenter cohort of 128 oral squamous cell carcinoma (OSCC) specimens from the tongue (OTSCC) using immunohistochemistry. In two external KLF4 mRNA datasets (The Cancer Genome Atlas/The Genotype‐Tissue Expression Portal), lower KLF4 mRNA expression was found in OSCC and head and neck squamous cell carcinomas (HNSCC) than in control oral epithelium. These data indicate that down‐regulation of KLF4 mRNA is linked to OSCC/HNSCC progression. Using Cox‐multivariate analysis, a significantly favorable 5‐year disease‐specific survival rate was observed for a subgroup of patients with a combination of high levels of KLF4 expression and inflammation. OSCC cell lines exposed to IFN‐γ showed a significant upregulation of nuclear KLF4 expression, indicating a link between inflammation and KLF4 expression in OSCC. Overall, the current data suggest a functional link between KLF4 and inflammation. The combination of high KLF4 nuclear expression and marked/moderate stromal inflammation might be useful as a favorable prognostic marker for a subgroup of OTSCC patients. [ABSTRACT FROM AUTHOR]

The competition between the impact of inherited weaknesses and plate kinematics determines the location and style of deformation during rifting, yet the relative impacts of these 'internal' and 'external' factors remain poorly understood, especially in 3D. In this study, we used brittle‐viscous analogue models to assess how multiphase rifting, that is changes in plate divergence rate or direction, and the presence and orientation of weaknesses in the competent mantle and crust, influences rift evolution. We find that the combined reactivation of mantle and crustal weaknesses without any kinematic changes already creates complex rift structures. Divergence rates affect the strength of the weak lower crustal layer and hence the degree of mantle‐crustal coupling; slow rifting decreases coupling, so that crustal weaknesses can dominate deformation localisation and surface structures, whereas fast rifting increases coupling and deformation related to mantle weaknesses can have a dominant surface expression. Through a change from slow to fast rifting mantle‐related deformation can overprint structures that previously formed along (differently oriented) crustal weaknesses. Conversely, a change from fast to slow rifting may shift deformation from mantle‐controlled towards crust‐controlled. When changing divergence directions, structures from the first rifting phase may control where subsequent deformation occurs, but only when they are sufficiently well developed. We furthermore place our results in a larger framework of brittle‐viscous rift modelling results from previous experimental studies, showing the importance of general lithospheric layering, divergence rate, the type of deformation in the mantle, and finally upper crustal structural inheritance. The interaction between these parameters can produce a variety of deformation styles that may, however, lead to comparable end products. Therefore, careful investigation of the distribution of strain localisation, and to an equal extent of basin depocenter locations over time is required to properly determine the evolution of complex rift systems, providing an incentive to revisit various natural examples. [ABSTRACT FROM AUTHOR]

Introduction. Anti-SAE1 antibodies have a low prevalence in dermatomyositis patients. Case Description. A 61-year-old woman presented with progressive shortness of breath, arthralgia, heliotrope rash, Gottron's papules, and erythematous rash. She had an interstitial lung disease (ILD) with a significant decrease in lung function. There was no muscle involvement. Immunological laboratory test results showed strongly positive anti-SAE1 antibodies. Glucocorticoid treatment resulted in remission of dermatomyositis. Conclusion. Anti-SAE antibodies in dermatomyositis patients are closely linked to unique clinical features. [ABSTRACT FROM AUTHOR]

The number of langerin‐expressing antigen‐presenting cells is higher in oral lichen planus than in normal oral mucosa. However, langerin may be expressed by several functionally different lineages of antigen presenting cells (APCs), and this has important implications for our understanding of the pathogenesis of oral lichen planus. The aim of this study was to determine the origin of the langerin‐expressing APCs. To this end, we examined oral mucosal biopsies from healthy persons and patients with oral lichen planus using multicolor immunofluorescence. In normal oral mucosa, a substantial fraction of Langerhans cells expressed Ki‐67, indicating that steady‐state oral mucosal Langerhans cells are at least partially maintained by self‐renewal. In oral lichen planus, the numbers of Langerhans cells were higher but proliferation was not altered, indicating that the higher cell numbers appeared to depend on recruited dendritic cell (DC)‐precursors. Moreover, we found a markedly higher number of langerin+ APCs within the lamina propria of oral lichen planus lesions. Such cells did not display monocyte‐ or macrophage markers, but rather showed a phenotype compatible with tissue‐elicited IRF4+ cDC2. Detailed understanding of how the oral mucosal APC network is regulated and the functional capacities of the different ontogenies may identify novel treatment targets for oral lichen planus. [ABSTRACT FROM AUTHOR]

We develop and test a mediation model linking job insecurity to affective commitment and psychosomatic complaints via two distinct theoretical mechanisms: fairness and energy depletion. Analyses were based on 6,268 Belgian bank employees facing organizational change. Results from structural equation modeling showed that fairness and exhaustion partially mediated the association of job insecurity with affective commitment and psychosomatic complaints, respectively. Multiple group analysis showed that the relation between job insecurity and fairness gradually decreased across the three change stages, and that the exhaustion process was most prominent amid the change. Implications and directions for future research are discussed. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

This paper presents an operator‐friendly and cost‐efficient approach to characterize the dielectric permittivity of liquids flowing in narrow tubes, such as drainage tubes used as part of the wound healing process in hospitals. The approach is based on an oscillator such that the characterization can be achieved with minimal operator (e.g., nurse) training. The oscillator's frequency is set by a 3D‐printed cavity resonator as to offer flexibility for the tube line to pass through. The oscillator design had to be tailored to ensure the oscillation condition to be met over a wide range of varying liquid compositions passing through the 3D‐printed cavity resonator. The design and results of a proof‐of‐concept implementation are presented and discussed. [ABSTRACT FROM AUTHOR]

Aim: Many of the current follow‐up schedules in a watch‐and‐wait approach include very frequent MRI and endoscopy examinations to ensure early detection of local regrowth (LR). The aim of this study was to analyse the occurrence and detection of LR in a watch‐and‐wait cohort and to suggest a more efficient follow‐up schedule. Method: Rectal cancer patients with a clinical complete response after neoadjuvant therapy were prospectively and retrospectively included in a multicentre watch‐and‐wait registry between 2004 and 2018, with the current follow‐up schedule with 3‐monthly endoscopy and MRI in the first year and 6 monthly thereafter. A theoretical comparison was constructed for the detection of LR in the current follow‐up schedule against four other hypothetical schedules. Results: In all, 50/304 (16%) of patients developed a LR. The majority (98%) were detected at ≤2 years, located in the lumen (94%) and were visible on endoscopy (88%). The theoretical comparison of the different hypothetical schedules suggests that the optimal follow‐up schedule should focus on the first 2 years with 3‐monthly endoscopy and 3–6 monthly MRI. Longer intervals in the first 2 years will cause delays in diagnosis of LR ranging from 0 to 5 months. After 2 years, increasing the interval from 6 to 12 months did not cause important delays. Conclusion: The optimal follow‐up schedule for a watch‐and‐wait policy in patients with a clinical complete response after chemoradiation for rectal cancer should include frequent endoscopy and to a lesser degree MRI in the first 2 years. Longer intervals, up to 12 months, can be considered after 2 years. [ABSTRACT FROM AUTHOR]

This article presents a novel 3D‐printed cavity resonator, adopted for the extraction of complex dielectric permittivity of liquid chemicals. The proposed structure consists of a spherical cavity slightly compressed at the poles (similar to a pumpkin), which embeds a thin pipe, where the liquid material under test flows. When the liquid is injected into the pipe, the resonance frequency and the quality factor of the fundamental cavity mode change, and their measurement allows retrieving the complex dielectric permittivity of the liquid. The device is entirely realized by 3D‐printing and subsequently metalized by electroplating. The flexibility of the 3D‐printing technique allows to implement cavities with unconventional shapes. In this case, the shape is selected to achieve a high quality factor, and it permits to find a good compromise between high sensitivity and good accuracy in the determination of the complex dielectric permittivity. The device was tested with several liquids, and the results were compared to characterizations performed using a commercial coaxial probe. [ABSTRACT FROM AUTHOR]

Aims: Because reported mortality on veno‐arterial (V‐A) extracorporeal life support (ECLS) substantially varies between centres, the aim of the current analysis was to assess the outcomes between units performing heart transplantation and/or implanting ventricular assist device (HTx/VAD) vs. non‐HTx/VAD units in patients undergoing V‐A ECLS for cardiogenic shock. Methods and results: Systematic search according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses was performed using PubMed/MEDLINE databases until 30 November 2019. Articles reporting in‐hospital/30‐day mortality and centre's HTx/VAD status were included. In‐hospital outcomes and long‐term survival were analysed in subgroup meta‐analysis. A total of 174 studies enrolling n = 13 308 patients were included with 20 series performed in non‐HTx/VAD centres (1016 patients, 7.8%). Majority of patients underwent V‐A ECLS for post‐cardiotomy shock (44.2%) and acute myocardial infarction (20.7%). Estimated overall in‐hospital mortality was 57.2% (54.9–59.4%). Mortality rates were higher in non‐HTx/VAD [65.5% (59.8–70.8%)] as compared with HTx/VAD centres [55.8% (53.3–58.2%)], P < 0.001. Estimated late survival was 61.8% (55.7–67.9%) without differences between non‐HTx/VAD and HTx/VAD centres: 66.5% (30.3–1.02%) vs. 61.7% (55.5–67.8%), respectively (P = 0.797). No differences were seen with respect to ECLS duration, limb complications, and reoperations for bleeding, kidney injury, and sepsis. Yet, weaning rates were higher in HTx/VAD vs. non‐HTx/VAD centres: 58.7% (56.2–61.1%) vs. 48.9% (42.0–55.9%), P = 0.010. Estimated rate of bridge to heart transplant was 6.6% (5.2–8.3%) with numerical, yet not statistically significant, difference between non‐HTx/VAD [2.7% (0.8–8.3%)] as compared with HTx/VAD [6.7% (5.3–8.6%)] (P = 0.131). Conclusions: Survival after V‐A ECLS differed according to centre's HTx/VAD status. Potentially different risk profiles of patients must be taken account for before definite conclusions are drawn. [ABSTRACT FROM AUTHOR]

Objective: Diagnosing autoimmune encephalitis (AIE) is difficult in patients with less fulminant diseases such as epilepsy. However, recognition is important, as patients require immunotherapy. This study aims to identify antibodies in patients with focal epilepsy of unknown etiology, and to create a score to preselect patients requiring testing. Methods: In this prospective, multicenter cohort study, adults with focal epilepsy of unknown etiology, without recognized AIE, were included, between December 2014 and December 2017, and followed for 1 year. Serum, and if available cerebrospinal fluid, were analyzed using different laboratory techniques. The ACES score was created using factors favoring an autoimmune etiology of seizures (AES), as determined by multivariate logistic regression. The model was externally validated and evaluated using the Concordance (C) statistic. Results: We included 582 patients, with median epilepsy duration of 8 years (interquartile range = 2–18). Twenty patients (3.4%) had AES, of whom 3 had anti–leucine‐rich glioma inactivated 1, 3 had anti–contactin‐associated protein‐like 2, 1 had anti–N‐methyl‐D‐aspartate receptor, and 13 had anti–glutamic acid decarboxylase 65 (enzyme‐linked immunosorbent assay concentrations >10,000IU/ml). Risk factors for AES were temporal magnetic resonance imaging hyperintensities (odds ratio [OR] = 255.3, 95% confidence interval [CI] = 19.6–3332.2, p < 0.0001), autoimmune diseases (OR = 13.31, 95% CI = 3.1–56.6, p = 0.0005), behavioral changes (OR 12.3, 95% CI = 3.2–49.9, p = 0.0003), autonomic symptoms (OR = 13.3, 95% CI = 3.1–56.6, p = 0.0005), cognitive symptoms (OR = 30.6, 95% CI = 2.4–382.7, p = 0.009), and speech problems (OR = 9.6, 95% CI = 2.0–46.7, p = 0.005). The internally validated C statistic was 0.95, and 0.92 in the validation cohort (n = 128). Assigning each factor 1 point, an antibodies contributing to focal epilepsy signs and symptoms (ACES) score ≥ 2 had a sensitivity of 100% to detect AES, and a specificity of 84.9%. Interpretation: Specific signs point toward AES in focal epilepsy of unknown etiology. The ACES score (cutoff ≥ 2) is useful to select patients requiring antibody testing. ANN NEUROL 2021;89:698–710 [ABSTRACT FROM AUTHOR]

PPARGC1A gene plays an important role in the activation of various important hormone receptors and transcriptional factors involved in the regulation of adaptive thermogenesis, gluconeogenesis, fiber-type switching in skeletal muscle, mitochondrial biogenesis, and adipogenesis, regulating the reproduction and proposed as a candidate gene for milk-related traits in cattle. This study identified polymorphisms in the PPARGC1A gene in Italian Mediterranean buffaloes and their associations to milk production and quality traits (lactation length, peak milk yield, fat and protein yield, and percentage). As a result, a total of seven SNPs (g.-78A>G, g.224651G>C, g.286986G>A, g.304050G>A, g.325647G>A, g.325817T>C, and g.325997G>A) were identified by DNA pooled sequencing. Analysis of productivity traits within the genotyped animals revealed that the g.286986G>A located at intron 4 was associated with milk production traits, but the g.325817T>C had no association with milk production. Polymorphisms in g.-78A>G was associated with peak milk yield and milk yield, while g.304050G>A and g.325997 G>A were associated with both milk yield and protein percentage. Our findings suggest that polymorphisms in the buffalo PPARGC1A gene are associated with milk production traits and can be used as a candidate gene for milk traits and marker-assisted selection in the buffalo breeding program. [ABSTRACT FROM AUTHOR]

Employee silence is detrimental to organizations, and managers high in narcissism may create conditions that indirectly promote employee silence. Drawing on socio‐analytic theory, in three samples (Ns = 79, 125, and 119), we investigated whether employees' perceptions of manager trustworthiness mediated the relation between manager trait narcissism and employee silence, and whether this mediation was moderated by a social skill, apparent sincerity. We found that the three samples largely supported our research model. Manager narcissism lowered employees' perceptions of manager trustworthiness, which were in turn related to increased employee silence. Whereas the effect of narcissism on trustworthiness perceptions and, indirectly, on employee silence were stronger for managers lower in apparent sincerity, these effects of narcissism were absent for managers high in apparent sincerity. Practitioner points: Perceptions of manager trustworthiness are a key relational process in dyadic, leader–follower relationships; for example, as our studies show, low trustworthiness predicts employee silence about important issues that may be hampering work/organizational functioning.Furthermore, our studies show that manager trait narcissism drives employees' perceptions of their manager's trustworthiness, and indirectly, employee silence.The findings highlight the downsides of manager narcissism in dyadic relationships with employees, which prompts guarding against hiring and promoting individuals who are high in trait narcissism to management positions.Moreover, we find that high narcissism managers who seek to appear sincere, may be successful at mitigating the impact of their narcissism on trustworthiness and silence.The findings lead us to recommend managers to improve their sincerity impression management skills – not doing so may be particularly detrimental among those who are more narcissistic. [ABSTRACT FROM AUTHOR]

Objectives: The presence of and the causative role of high‐risk human papilloma virus (HPV) is a subject of controversy in oral squamous cell carcinoma (OSCC). The disagreement can be related to the misclassification of OSCC as oropharyngeal squamous cell carcinoma and/or lack of standard detection methods. This study aimed to examine the presence of transcriptionally active high‐risk HPV in a homogenous Norwegian cohort of primary and second primary OSCC of the mobile tongue (oral tongue squamous cell carcinoma—OTSCC). Methods: Tissue microarrays containing formalin‐fixed and paraffin‐embedded cores of 146 OTSCC from the anterior 2/3 of the tongue (n = 128 primary and n = 18 second primary) from a multicentric Norwegian cohort were examined for the presence of high‐risk HPV by DNA‐ and RNA‐in situ hybridization (ISH) assays and p16 immunohistochemistry. Results: Transcriptionally active HPV (E6/E7 mRNA) was not identified in any of the OTSCC specimens. In parallel, no tumors were positive for HPV by DNA ISH. Although, 61 (42%) OTSCC demonstrated p16 positivity with varying staining intensity and subcellular localization, only two cases demonstrated strong and uniform p16‐staining (both cytoplasmic and nuclear) in >70% of cancer cells. The absence of transcriptionally active high‐risk HPV in this cohort of OTSCC indicates that high‐risk HPV is an unlikely causative factor in the present material. [ABSTRACT FROM AUTHOR]

The present study examined employee-involvement climate (i.e., information-sharing and decision-making climate) as a moderator of the relationship between pay-level satisfaction and employee outcomes (i.e., job satisfaction, affective commitment, and turnover intention). Survey data were collected from 22,662 Belgian employees, representing 134 organizations. The hypotheses derived from distributive justice theory and from research on the meaning of pay received partial support. Multilevel analyses revealed that a decision-making climate buffered the negative effects of low pay-level satisfaction, and that an information-sharing climate exacerbated the negative effects of low pay-level satisfaction. Theoretical and practical implications of this differential moderating effect are discussed. [ABSTRACT FROM AUTHOR]

Objective: To investigate if cerebroplacental ratio (CPR) adds to the predictive value of umbilical artery pulsatility index (UA PI) alone - standard of practice - for adverse perinatal outcome in singleton pregnancies.Design and Setting: Meta-analysis based on individual participant data (IPD).Population or Sample: Ten centres provided 17 data sets for 21 661 participants, 18 731 of which could be included. Sample sizes per data set ranged from 207 to 9215 individuals. Patient populations varied from uncomplicated to complicated pregnancies.Methods: In a collaborative, pooled analysis, we compared the prognostic value of combining CPR with UA PI, versus UA PI only and CPR only, with a one-stage IPD approach. After multiple imputation of missing values, we used multilevel multivariable logistic regression to develop prediction models. We evaluated the classification performance of all models with receiver operating characteristics analysis. We performed subgroup analyses according to gestational age, birthweight centile and estimated fetal weight centile.Main Outcome Measures: Composite adverse perinatal outcome, defined as perinatal death, caesarean section for fetal distress or neonatal unit admission.Results: Adverse outcomes occurred in 3423 (18%) participants. The model with UA PI alone resulted in an area under the curve (AUC) of 0.775 (95% CI 0.709-0.828) and with CPR alone in an AUC of 0.778 (95% CI 0.715-0.831). Addition of CPR to the UA PI model resulted in an increase in the AUC of 0.003 points (0.778, 95% CI 0.714-0.831). These results were consistent across all subgroups.Conclusions: Cerebroplacental ratio added no predictive value for adverse perinatal outcome beyond UA PI, when assessing singleton pregnancies, irrespective of gestational age or fetal size.Tweetable Abstract: Doppler measurement of cerebroplacental ratio in clinical practice has limited added predictive value to umbilical artery alone. [ABSTRACT FROM AUTHOR]

The purpose of this invited paper is to give readers a critical and comprehensive overview on how to extract dielectric properties of a bioliquid within a broad frequency range. Two sensors are used in the paper to characterize saline solutions by measuring the broadband complex permittivity. The two sensors are based on transmission line and interdigital electrodes designed for low‐ and high‐ frequency measurements, respectively, on the basis of the coplanar waveguide structure due to its convenience of fabrication and integration with microfluidic structures for liquid measurements. Different from traditional work where the finite element simulation method is used, the characterization theories of the two sensors are built based on a numerical modeling procedure, which can dramatically increase the device design efficiency, taking just a few seconds. Differently from the finite element method, the proposed numerical analysis utilizes a conformal mapping technique for both sensors. The characterization theories of the two sensors are validated by measuring de‐ionized water. The platform is finally used to measure 0.1 and 0.5 mol/L saline solutions within a broadband frequency range going from 10 up to 50 GHz, with the repeatability error within 5%. [ABSTRACT FROM AUTHOR]

Aim: Connective tissue changes due to ageing or diseases leading to changes in the colonic wall are one theory for the development of diverticula. Alpha‐1‐antitrypsin (A1AT), a protease inhibitor that protects connective tissue, possibly plays a role in the aetiology of diverticulosis. The aim of this study was to explore associations between the development of diverticula and A1AT deficiency. Methods: This was a multicentre prospective case–control study. A total of 221 patients aged ≥ 60 years with acute abdominal pain undergoing abdominal CT were included and analysed. Patients with diverticula were defined as the research group, patients without diverticula as controls. Genotype analysis for A1AT deficiency was performed. Results: Twenty‐six of 221 (11.8%) patients were diagnosed with (being a carrier of) A1AT deficiency. A non‐significant difference in prevalence between patients with and without diverticula was found, 20 (13.9%) of 144 vs 6 (7.8%) of 77, respectively, with a crude OR of 1.9 (95% CI 0.7–5.0; P = 0.186) and after adjustment for confounders an adjusted OR of 1.5 (95% CI 0.5–4.0; P = 0.466). A non‐significant difference in 30‐day mortality rate from acute diverticulitis between A1AT deficient patients (or carriers) and those without was observed: two (22.2%) of nine patients with A1AT deficiency vs 1 (1.8%) of 55 without. Conclusion: We found no convincing evidence that A1AT deficiency plays a role in the aetiology of diverticulitis, although deficient patients and carriers had a higher mortality when experiencing diverticulitis. Diverticulitis is a multifactorial disease and larger numbers may be needed to explore the role of A1AT deficiency among other contributing factors. [ABSTRACT FROM AUTHOR]

Objective: Psychosocial interventions can reduce cancer‐related fatigue effectively. However, it is still unclear if intervention effects differ across subgroups of patients. These meta‐analyses aimed at evaluating moderator effects of (a) sociodemographic characteristics, (b) clinical characteristics, (c) baseline levels of fatigue and other symptoms, and (d) intervention‐related characteristics on the effect of psychosocial interventions on cancer‐related fatigue in patients with non‐metastatic breast and prostate cancer. Methods: Data were retrieved from the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) consortium. Potential moderators were studied with meta‐analyses of pooled individual patient data from 14 randomized controlled trials through linear mixed‐effects models with interaction tests. The analyses were conducted separately in patients with breast (n = 1091) and prostate cancer (n = 1008). Results: Statistically significant, small overall effects of psychosocial interventions on fatigue were found (breast cancer: β = −0.19 [95% confidence interval (95%CI) = −0.30; −0.08]; prostate cancer: β = −0.11 [95%CI = −0.21; −0.00]). In both patient groups, intervention effects did not differ significantly by sociodemographic or clinical characteristics, nor by baseline levels of fatigue or pain. For intervention‐related moderators (only tested among women with breast cancer), statistically significant larger effects were found for cognitive behavioral therapy as intervention strategy (β = −0.27 [95%CI = −0.40; −0.15]), fatigue‐specific interventions (β = −0.48 [95%CI = −0.79; −0.18]), and interventions that only targeted patients with clinically relevant fatigue (β = −0.85 [95%CI = −1.40; −0.30]). Conclusions: Our findings did not provide evidence that any selected demographic or clinical characteristic, or baseline levels of fatigue or pain, moderated effects of psychosocial interventions on fatigue. A specific focus on decreasing fatigue seems beneficial for patients with breast cancer with clinically relevant fatigue. [ABSTRACT FROM AUTHOR]

Oral lichen planus (OLP) is a chronic inflammatory disease displaying ultrastructural disturbances in epithelial hemidesmosomes. The expression of several key hemidesmosomal components in OLP as well as in normal buccal mucosa is, however, unknown. The aim of the study was therefore to examine intracellular and extracellular components involved in hemidesmosomal attachment, in OLP (n = 20) and in normal buccal mucosa (n = 10), by immunofluorescence. In normal buccal mucosa, laminin‐α3γ2, integrin‐α6β4, CD151, collagen α‐1(XVII) chain, and dystonin showed linear expression along the basal membrane, indicating the presence of type I hemidesmosomes. Plectin stained most epithelial cell membranes and remained unphosphorylated at S4642. In OLP, most hemidesmosomal molecules examined showed disturbed expression consisting of discontinuous increases, apicolateral location, and/or intracellular accumulation. Plectin showed S4642‐phosphorylation at the basement membrane, and deposits of laminin‐α3 and laminin‐γ2 were found within the connective tissue. The disturbed expression of hemidesmosomal proteins in OLP indicates deficient attachment of the basal cell layer, which can contribute to detachment and cell death of basal keratinocytes seen in the disease. [ABSTRACT FROM AUTHOR]

Objectives: The conceptual approach of compassion underlying compassion‐focused therapy (CFT) is based on theoretical rather than empirical grounds. The aim of the present study was to seek empirical support for components of compassion as outlined in the theoretical model underpinning CFT, and to explore which components, if any, matter most for improving well‐being. Design: A sequential exploratory mixed methods design was employed. Methods: Alongside a randomized controlled trial (RCT), we systematically examined 625 emails sent by 87 RCT participants to five counsellors during the course of a well‐being enhancing CFT self‐help intervention, to identify theoretically based compassionate attributes and skills. Next, in a quantitative analysis, we compared participants who did and did not show clinically relevant improvement on well‐being with regard to the occurrence of compassionate attributes and skills. Results: Although the theoretical model of compassion integral to CFT was largely supported by the emails, it was slightly simplified so as to better fit the data. The adjusted model comprises five compassionate attributes (i.e., care for well‐being, sensitivity, empathy, distress tolerance, and common humanity) and four compassionate skills (i.e., compassionate attention, reasoning, behaviour, and feeling/sensation). Three illustrative cases are presented to contribute to a better understanding of fundamental components of compassion. Quantitative analyses indicate that participants showing clinically relevant improvement on well‐being expressed significantly more compassionate feeling/sensation compared to those who did not. Conclusions: We found preliminary evidence for the conceptualization of compassion underlying CFT. Compassionate feeling/sensation bears particular interest when well‐being is the intended outcome of CFT. Practitioner points: Individuals participating in compassion‐focused therapy for enhancing well‐being experience a wide range of compassionate attributes and skills.Compassion‐focused therapy may instigate well‐being if a client is able to experience compassionate feeling/sensation. [ABSTRACT FROM AUTHOR]

The V-Akt Murine Thymoma Viral Oncogene Homolog 3 (AKT3) gene is of the serine/threonine-protein kinase family and influences the production of milk fats and cholesterol by acting on the sterol administrative area restricting protein (SREBP). The AKT3 gene is highly preserved in animals, and during lactation in cattle, its expression increases. The AKT3 gene is expressed in the digestive system, mammary gland, and immune cells. A phylogenetic investigation was performed to clarify the evolutionary role of AKT3, by maximum probability. The AKT3 gene sequence data of various mammalian species was evident even with animals undergoing breeding selection. From 39 mammalian species studied, there was a signal of positive diversifying selection with Hominidae at 13Q, 16G, 23R, 24P, 121P, 294K, 327V, 376L, 397K, 445T, and 471F among other codon sites of the AKT3 gene. These sites were codes for amino acids such as arginine, proline, lysine, and leucine indicating major roles for the function of immunological proteins, and in particular, the study highlighted the importance of changes in gene expression of AKT3 on immunity. [ABSTRACT FROM AUTHOR]

Objective: Selective IgA deficiency (sIgAD) is the most common primary immunodeficiency in Western countries. Patients can suffer from recurrent infections and autoimmune diseases because of a largely unknown aetiology. To increase insights into the pathophysiology of the disease, we studied memory B and T cells and cytokine concentrations in peripheral blood. Methods: We analysed 30 sIgAD patients (12 children, 18 adults) through detailed phenotyping of peripheral B‐cell, CD8+ T‐cell and CD4+ T‐cell subsets, sequence analysis of IGA and IGG transcripts, in vitro B‐cell activation and blood cytokine measurements. Results: All patients had significantly decreased numbers of T‐cell‐dependent (TD; CD27+) and T‐cell‐independent (TI; CD27−) IgA memory B cells and increased CD21low B‐cell numbers. IgM+IgD− memory B cells were decreased in children and normal in adult patients. IGA and IGG transcripts contained normal SHM levels. In sIgAD children, IGA transcripts more frequently used IGA2 than controls (58.5% vs. 25.1%), but not in adult patients. B‐cell activation after in vitro stimulation was normal. However, adult sIgAD patients exhibited increased blood levels of TGF‐β1, BAFF and APRIL, whereas they had decreased Th1 and Th17 cell numbers. Conclusion: Impaired IgA memory formation in sIgAD patients is not due to a B‐cell activation defect. Instead, decreased Th1 and Th17 cell numbers and high blood levels of BAFF, APRIL and TGF‐β1 might reflect disturbed regulation of IgA responses in vivo. These insights into B‐cell extrinsic immune defects suggest the need for a broader immunological focus on genomics and functional analyses to unravel the pathogenesis of sIgAD. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to provide a comprehensive overview of the field‐effect transistor (FET) small‐signal modeling using artificial neural networks (ANNs). To gain an in‐depth insight into how to effectively develop an ANN model, we present a comparative study on the application of the ANNs for modeling the scattering (S‐) parameters of a variety of FET technologies versus bias point, ambient temperature, and geometrical dimensions. As will be shown, the main challenge consists of identifying the most appropriate ANN model for the specific case under study. This is because the performance of an ANN‐based model can vary significantly, depending especially on the choice of the model structure and the size and parameters of the chosen ANN. In addition, the choice of the model is related directly to the behavior of the FET characteristics, which might greatly depend on the selected device technology and operating conditions. The analysis of the present comparative study allows understanding how to properly construct ANN models to perform at their best for a successful FET modeling. [ABSTRACT FROM AUTHOR]

Keratins form intermediate filaments of the cytoskeleton in keratinocytes and have roles in cell structure, signaling, intracellular transport, and cell death. Oral lichen planus (OLP) is an oral inflammatory disease with derangements in basal keratinocytes and disruption of the basal membrane. Here, we focused on epithelial expression of keratins 8, 18, and 19 because these proteins are known to modulate cell death. Biopsies were taken from buccal oral mucosa of persons with normal oral mucosa (n = 10) or atrophic OLP (n = 10). Cultured normal oral keratinocytes (n = 4) showed expression of mRNA and protein for keratins 8, 18, and 19. Immunohistochemistry showed consistent staining for keratins 8 and 18 in basal keratinocytes of normal oral mucosa. In OLP, staining for keratin (K)8 was mostly negative and staining for K18 was weak. Keratin 19 was expressed irregularly in most biopsies of normal oral mucosa and not at all in OLP. Several mononuclear leukocytes in the cellular infiltrate showed membrane staining for K8 and K18. Positive staining for K16 confirmed partial collapse of the basal cell layer in OLP. The basal cell niche in OLP therefore appeared to be partly populated with keratinocytes demonstrating a higher degree of differentiation (K8− K18− K19− K16+); consequently, such areas may be more susceptible to the action of cell death factors released from the cell infiltrate as a result of lacking the protective, normal keratin present in the basal epithelial cell layer of normal oral mucosa. [ABSTRACT FROM AUTHOR]

Objective: Doppler ultrasonographic assessment of the cerebroplacental ratio (CPR) and middle cerebral artery (MCA) is widely used as an adjunct to umbilical artery (UA) Doppler to identify fetuses at risk of adverse perinatal outcome. However, reported estimates of its accuracy vary considerably. The aim of this study was to review systematically the prognostic accuracies of CPR and MCA Doppler in predicting adverse perinatal outcome, and to compare these with UA Doppler, in order to identify whether CPR and MCA Doppler evaluation are of added value to UA Doppler.Methods: PubMed, EMBASE, the Cochrane Library and ClinicalTrials.gov were searched, from inception to June 2016, for studies on the prognostic accuracy of UA Doppler compared with CPR and/or MCA Doppler in the prediction of adverse perinatal outcome in women with a singleton pregnancy of any risk profile. Risk of bias and concerns about applicability were assessed using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) tool. Meta-analysis was performed for multiple adverse perinatal outcomes. Using hierarchal summary receiver-operating characteristics meta-regression models, the prognostic accuracy of CPR vs MCA Doppler was compared indirectly, and CPR and MCA Doppler vs UA Doppler compared directly.Results: The search identified 4693 articles, of which 128 studies (involving 47 748 women) were included. Risk of bias or suboptimal reporting was detected in 120/128 studies (94%) and substantial heterogeneity was found, which limited subgroup analyses for fetal growth and gestational age. A large variation was observed in reported sensitivities and specificities, and in thresholds used. CPR outperformed UA Doppler in the prediction of composite adverse outcome (as defined in the included studies) (P < 0.001) and emergency delivery for fetal distress (P = 0.003), but was comparable to UA Doppler for the other outcomes. MCA Doppler performed significantly worse than did UA Doppler in the prediction of low Apgar score (P = 0.017) and emergency delivery for fetal distress (P = 0.034). CPR outperformed MCA Doppler in the prediction of composite adverse outcome (P < 0.001) and emergency delivery for fetal distress (P = 0.013).Conclusion: Calculating the CPR with MCA Doppler can add value to UA Doppler assessment in the prediction of adverse perinatal outcome in women with a singleton pregnancy. However, it is unclear to which subgroup of pregnant women this applies. The effectiveness of the CPR in guiding clinical management needs to be evaluated in clinical trials. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

In this article, the authors used a within-person design to examine the relationship between job insecurity and employee in-role and extra-role performance, and the buffering role of time-varying work-based support (i.e., supervisor and colleague support) in this relationship. Weekly diary data gathered over the course of three weeks from 56 employees confronted with organizational restructuring and analyzed with a hierarchical linear modeling approach showed that weekly fluctuations in job insecurity negatively predicted week-level in-role performance. As predicted, supervisor support moderated the intra-individual relationship between job insecurity and in-role performance, so that employees' in-role performance suffered less from feeling job insecurity during weeks in which they received more support from their supervisor. No relationship between job insecurity and extra-role performance was observed. This within-person study contributes to research on job insecurity that has primarily focused on inter-individual differences in job insecurity and their associations with job performance. Theoretical and practical implications for human resource management are discussed. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]