bluuebunny/crossref_metadata_2025 huggingface dataset:
Cleavage of 14-3-3ε by the enteroviral 3C protease dampens RIG-I mediated antiviral signaling
Authors: Andrews Daniel D.T. , Mohamud Yasir , Vlok Marli , Bani Dorssa Akbari , Hay Brenna N. , Foster Leonard J. , Luo Honglin , Overall Christopher M. , Jan Eric
Published: September 2022

Viruses have evolved diverse strategies to evade the host innate immune response and promote infection. The RIG-I-like-receptors RIG-I and MDA5 (RLRs) are antiviral factors that sense viral RNA and signal downstream via mitochondrial antiviral-signaling protein (MAVS) to activate type I interferon (IFN) expression. 14-3-3ε is a key component of the RIG-I translocon complex that interacts with MAVS at the mitochondrial membrane; however, the exact role of 14-3-3ε in this pathway is not well understood. In this study, we demonstrate that 14-3-3ε is a direct substrate of both the poliovirus and coxsackievirus B3 (CVB3) 3C proteases (3Cpro), and that it is cleaved at Q236↓G237, resulting in the generation of N- and C-terminal fragments of 27.0 and 2.1 kDa, respectively. Expression of the N-terminal cleavage fragment in cells reduces IFNB mRNA production during poly(I:C) stimulation, thus suggesting an antagonistic effect in the presence of the endogenous 14-3-3ε protein. The N-terminal 14-3-3ε fragment does not interact with RIG-I in co-immunoprecipitation assays, nor can it facilitate RIG-I translocation to the mitochondria. Probing the intrinsically disordered C-terminal region identifies key residues responsible for RIG-I signaling. Finally, overexpression of the N-terminal fragment promotes CVB3 infection and influenza A virus (H1N1) RNA production and reduces IFNB mRNA production during infection. The strategic enterovirus 3Cpro-mediated cleavage of 14-3-3ε antagonizes RIG-I signaling by disrupting critical interactions within the RIG-I translocon complex, thus contributing to evasion of the host antiviral response.

Author Summary

Host antiviral factors work to sense virus infection through various mechanisms, including a complex signaling pathway known as the RIG-I like receptor (RLR) pathway. This pathway drives the production of antiviral molecules known as interferons, which are necessary to establish an antiviral state in the cellular environment. Key to this antiviral signaling pathway is the small chaperone protein 14-3-3ε, which facilitates the delivery of a viral sensor protein, RIG-I, to the mitochondria. In this study, we show that the enteroviral 3C protease cleaves 14-3-3ε during infection, rendering it incapable of facilitating this antiviral response. We also find that the cleavage fragment inhibits RIG-I signaling and promotes virus infection. Our findings reveal a novel viral strategy that restricts the antiviral host response and provides insights into the mechanisms underlying 14-3-3ε function in RIG-I antiviral signaling.
Mosquito Electroantennogram Recordings
Authors: Lahondère Chloé
Published: September 2022

Electroantennography (EAG) is a simple, yet powerful technique that can be used to indicate that chemical compounds are detected by mosquito antennae. When coupled with gas chromatography (GC), it allows for the identification of detectable compounds within complex mixtures, including those in plant and animal headspaces that might influence mosquito behavior. EAGs and GC-EAGs reveal compounds that can be tested in behavioral assays with the goal of developing new repellents or attractants for mosquito control.
The interaction of corporate social responsibility (CSR) materiality and explicit assessment on willingness to invest: perception of financial analysts
Authors: Pratoomsuwan Thanyawee , Chiaravutthi Yingyot
Published: September 2022

Purpose

Recent research finds that the effect of corporate social responsibility (CSR) information, especially when CSR is not related to core business activities (immaterial CSR issues), on investment decisions will be eliminated when it is explicitly assessed. As CSR expectations from investors appear to be different across specific cultures and countries (Van der Laan Smith et al., 2010), we aim to investigate (1) the effect of CSR materiality on investors' willingness to invest and (2) how the explicit assessment of CSR information moderates the effect of explicit assessment and CSR materiality on investment judgment by professional investors in Thailand.

Design/methodology/approach

A 2 × 2 between-subject experiment was conducted based on 136 professional investors.

Findings

Overall, the results suggest that an investor's willingness to invest is greater when CSR is material than when CSR is immaterial. In addition, the assessment of willingness to invest in a firm's stock is not affected by the presence or absence of explicit assessment of the material CSR. However, the results suggest that when CSR issues are immaterial, explicit assessment significantly removes the effect of CSR performance on the investor's investment judgment. Consistent with the findings from Guiral et al. (2019), professional investors seem to process CSR information in a similar way as nonprofessional investors.

Practical implications

The findings suggest that material CSR information has a significant impact on the investment decisions of professional investors. This is consistent with the materiality guidance provided by the Sustainability Accounting Standard Board (SASB) as helpful in improving the value of CSR information for investors. These results should be of interest to both business people and regulators because, despite differences in the cultural and audit environment, the results confirm that professional investors in Thailand use CSR information in an experimental setting, thereby providing some evidence of value creation from CSR activities and nonfinancial disclosures.

Originality/value

While recent experimental research has primarily examined how nonprofessional investors evaluate CSR information in Western countries, this study extends the literature by focusing on professional investors in emerging capital markets and how they use CSR information in their investment decisions (Coram et al., 2009). The study also addresses the call for research on differences in CSR reporting and practices in different cultures and countries (Van der Laan Smith et al., 2010; Coram et al., 2009) to provide insights into how professional investors in Thailand use CSR information to formulate investment judgments.
Do online reviews help? The contingent effect of perceived crowdedness and gender for restaurant selection
Authors: Ali Muhammad Asghar , Ting Ding Hooi , Azeem Muhammad Umer , Abbasi Amir Zaib
Published: September 2022

Purpose

This paper aims to investigate the impact of perceived usefulness of online reviews and crowd cues on restaurant selection. In addition, the authors also examine the moderating role of perceived crowding and gender in this process.

Design/methodology/approach

The proposed hypotheses were tested with survey data (N = 200) collected from customers visiting full-service restaurants in Malaysia. The data were analyzed using SEM through Smart PLS.

Findings

The findings supported that the perceived usefulness of online reviews and perceived crowding have a positive effect on a consumer's purchase intentions, i.e. their decision of restaurant selection. Besides, a higher level of perceived crowding strengthens the relationship between the perceived usefulness of online reviews and their purchase intentions. This finding delineates that consumers prefer to dine in a crowded place with useful online reviews in an unfamiliar place. Finally, the results show that the effect of the usefulness of online reviews on purchase intentions does not vary with respect to gender (no significant contingent effect). However, the effect of perceived crowding varies with respect to gender – male customers have higher intentions to join crowded restaurants as compared to females.

Research limitations/implications

Limitation of this study is its cross-sectional research design; data were collected in a single time frame. Longitudinal research design can be used to get in-depth knowledge of this phenomenon. Secondly, a non-probability sampling technique was used in this study, future research can used probability sampling technique to enhance generalizability of the study. Moreover, this study focused on the human crowding aspect, future studies can cover both aspects of crowding (human crowding and spatial crowding) in retailing or other service sectors (Blut and Iyer, 2020).

Practical implications

This study has multiple practical implications.

Originality/value

This study extends the current research on usefulness of online reviews and perceived crowding by investigating its direct and conditional effects. Specifically, the authors contribute in extant research by explaining its differential effects for male and female customers, when they select which restaurants to dine.
Financial support for households and the demand for child protection services – a municipality-level analysis of income support for single-parent households and reimbursements for depression medicines
Authors: Häkkilä Laura , Seppälä Piia , Hietamäki Juulia , Toikko Timo
Published: September 2022

Purpose

The study covers two different forms of financial support for households, income support for single parents and reimbursements for depression medicines, and explores their relationships with the demand for child protection services.

Design/methodology/approach

The data were retrieved from the Sotkanet, the Finnish Indicator Bank, and included 292 Finnish municipalities. It was hypothesised that the effect of income support for single-parent households on the need for child protection is mediated by reimbursements for depression medicines. The hypotheses were tested by using a conditional process analysis program, PROCESS (Model 4).

Findings

It was found that income support reduces the proportion of reimbursements for depression medicines in a municipality, which in turn reduces the need for child protection services. At the level of social policy, the study tentatively suggests that the social welfare system may affect the demand for child protection by investing in income support for single-parent households.

Research limitations/implications

The choice of variables does not fully explain the effect of the mechanism. The relationships that are found in this study can have hidden factors which affect them. Further, the data have only 292 cases, which is quite a small sample, and is limited to Finland.

Originality/value

The study suggests that the social welfare system may affect the demand for child protection by investing in income support for single-parent households.
Composite collaboration and the differentiation strategies adopted by emerging market firms in advanced markets during the COVID-19 pandemic
Authors: Khan Huda
Published: September 2022

Purpose

This article illustrates how, during the COVID-19 pandemic, emerging market exporting firms can adopt differentiation strategies using composition-based capabilities, which, in turn, will enable them to strengthen their images and market shares, i.e. their strategic marketing performance in advanced markets.

Design/methodology/approach

This study is based on survey data obtained from 86 Pakistani firms exporting to advanced economies.

Findings

The study found that compositional collaboration capabilities positively influence the differentiation strategies and strategic marketing performance of emerging market exporting firms conducting business in advanced host markets. Furthermore, the findings indicate that differentiation strategies mediate the influence of compositional collaboration capabilities on the strategic marketing performance of these firms.

Originality/value

By taking a new compositional based theoretical perspective, this study examined the underexplored phenomenon of how emerging market firms can differentiate their offerings in advanced export markets in order to achieve a better strategic performance during external shocks such as the COVID-19 pandemic. Given that export growth is a strategic priority for many emerging markets, including Pakistan, due to their substantial trade deficits, this study provides important contributions from both the theoretical and practical perspectives.
What innovations would enable the tourism and hospitality industry in the Caribbean to re-build?
Authors: Crick Anne P.
Published: September 2022

Purpose

The purpose of this article is to identify the opportunities for resetting Caribbean tourism along the lines of sustainability, the use of SMART technology and social inclusion so that it benefits all of its stakeholders.

Design/methodology/approach

This is a conceptual paper that draws on research about the limitations of Caribbean tourism and the emerging needs of tourism stakeholders in the wake of the Covid-19 pandemic.

Findings

The paper proposes five areas of focus - educating smartly, becoming a smart and strategic employer, using technology smartly to identify value and values of internal and external customers, thinking, buying, using sustainably and connecting the dots in joined up government.

Research limitations/implications

The paper draws on current research on problems associated with pre-pandemic tourism and proposes ways that these can be addressed. It utilizes the service-profit chain model to identify the relationships between internal and external service value.

Practical implications

Caribbean tourism interests have the choice of using the pandemic as an enforced pause or an opportunity to reset. This paper assumes the latter choice and makes specific recommendations for private and public sector interests to shape a sector that is socially inclusive and sustainable and that incorporates smart technology.

Social implications

The Caribbean is the world's most tourism dependent region but a critical examination indicates that the pursuit of tourist numbers and dollars has come at a cost to local residents. The paper utilizes the new three Ss of smart destinations, social inclusion and sustainability to recommend ways in which tourism can better serve the region and a new generation of tourists.

Originality/value

Tourism in the Caribbean has grown exponentially but not always in a way that benefits all of its stakeholders. Covid-19 forced a cessation of most activities and created an opportunity to rethink tourism. This paper recognizes that the changing needs of external and internal stakeholders must be considered if tourism is to be successful and sustainable, and proposes five overlapping and important innovations.
Fluoro‐recognition: New in vivo fluorescent assay for toluene dioxygenase probing induction by and metabolism of polyfluorinated compounds
Authors: Aukema Kelly G. , Bygd Madison D. , Tassoulas Lambros J. , Richman Jack E. , Wackett Lawrence P.
Published: September 2022

The present study examined the regulatory and metabolic response of the aromatic degrader Pseudomonas putida F1 and its tod operon, controlling toluene degradation, to fluorinated aromatic and aliphatic compounds. The tod operon is upregulated by inducer binding to the TodS sensing domain of a two‐component regulator. The induced enzymes include toluene dioxygenase that initiates catabolic assimilation of benzenoid hydrocarbons. Toluene dioxygenase was shown to oxidize 6‐fluoroindole to a meta‐stable fluorescent product, 6‐fluoroindoxyl. The fluorescent output allowed monitoring relative levels of tod operon induction in whole cells using microtiter well plates. Mono‐ and polyfluorinated aromatic compounds were shown to induce toluene dioxygenase, in some cases to a greater extent than compounds serving as growth substrates. Compounds that are oxidized by toluene dioxygenase and undergoing defluorination were shown to induce their own metabolism. 1,2,4‐Trifluorobenzene caused significant induction and computational modelling indicated productive binding to the TodS sensor domain of the TodST regulator. Toluene dioxygenase also showed preferential binding of 1,2,4‐trifluorobenzene such that defluorination was favoured. Fluorinated aliphatic compounds were shown to induce toluene dioxygenase. An aliphatic ether with seven fluorine atoms, 1,1,1,2‐tetrafluoro‐2‐trifluoromethoxy‐4‐iodobutane (TTIB), was an excellent inducer of toluene dioxygenase activity and shown to undergo transformation in cultures of P. putida F1.
Detecting and reducing heterogeneity of error in acoustic classification
Authors: Metcalf Oliver C. , Barlow Jos , Bas Yves , Berenguer Erika , Devenish Christian , França Filipe , Marsden Stuart , Smith Charlotte , Lees Alexander C.
Published: September 2022

Passive acoustic monitoring can be an effective method for monitoring species, allowing the assembly of large audio datasets, removing logistical constraints in data collection and reducing anthropogenic monitoring disturbances. However, the analysis of large acoustic datasets is challenging and fully automated machine learning processes are rarely developed or implemented in ecological field studies. One of the greatest uncertainties hindering the development of these methods is spatial generalisability—can an algorithm trained on data from one place be used elsewhere?

We demonstrate that heterogeneity of error across space is a problem that could go undetected using common classification accuracy metrics. Second, we develop a method to assess the extent of heterogeneity of error in a random forest classification model for six Amazonian bird species. Finally, we propose two complementary ways to reduce heterogeneity of error, by (i) accounting for it in the thresholding process and (ii) using a secondary classifier that uses contextual data.

We found that using a thresholding approach that accounted for heterogeneity of precision error reduced the coefficient of variation of the precision score from a mean of 0.61 ± 0.17 (SD) to 0.41 ± 0.25 in comparison to the initial classification with threshold selection based on F‐score. The use of a secondary, contextual classification with thresholding selection accounting for heterogeneity of precision reduced it further still, to 0.16 ± 0.13, and was significantly lower than the initial classification in all but one species. Mean average precision scores increased, from 0.66 ± 0.4 for the initial classification, to 0.95 ± 0.19, a significant improvement for all species.

We recommend assessing—and if necessary correcting for—heterogeneity of precision error when using automated classification on acoustic data to quantify species presence as a function of an environmental, spatial or temporal predictor variable.
Hungary: Political Developments and Data in 2021
Authors: VÁRNAGY RÉKA
Published: September 2022

The Hungarian governing party Fidesz maintained a state of emergency in 2021, but aside from the pandemic, it focused on setting the tone for the 2022 elections and on developing a new communication strategy targeting sexual minorities. Regarding the institutional framework, the restructuration of higher education is highlighted in the article. The main opposition primaries, which took place in the fall, are also discussed. The text offers an insight into the political dynamic of opposition parties and presents basic data about the primaries.
Point‐of‐care echocardiography of the right heart improves acute heart failure risk stratification for low‐risk patients: The REED‐AHF prospective study
Authors: Harrison Nicholas E. , Favot Mark J. , Gowland Laura , Lenning Jacob , Henry Sarah , Gupta Sushane , Abidov Aiden , Levy Phillip , Ehrman Robert
Published: September 2022

Objectives

Validated acute heart failure (AHF) clinical decision instruments (CDI) insufficiently identify low‐risk patients meriting consideration of outpatient treatment. While pilot data show that tricuspid annulus plane systolic excursion (TAPSE) is associated with adverse events, no AHF CDI currently incorporates point‐of‐care echocardiography (POCecho). We evaluated whether TAPSE adds incremental risk stratification value to an existing CDI.

Methods

Prospectively enrolled patients at two urban‐academic EDs had POCechos obtained before or <1 h after first intravenous diuresis, positive pressure ventilation, and/or nitroglycerin. STEMI and cardiogenic shock were excluded. AHF diagnosis was adjudicated by double‐blind expert review. TAPSE, with an a priori cutoff of ≥17 mm, was our primary measure. Secondary measures included eight additional right heart and six left heart POCecho parameters. STRATIFY is a validated CDI predicting 30‐day death/cardiopulmonary resuscitation, mechanical cardiac support, intubation, new/emergent dialysis, and acute myocardial infarction or coronary revascularization in ED AHF patients. Full (STRATIFY + POCecho variable) and reduced (STRATIFY alone) logistic regression models were fit to calculate adjusted odds ratios (aOR), category‐free net reclassification index (NRIcont), ΔSensitivity (NRIevents), and ΔSpecificity (NRInonevents). Random forest assessed variable importance. To benchmark risk prediction to standard of care, ΔSensitivity and ΔSpecificity were evaluated at risk thresholds more conservative/lower than the actual outcome rate in discharged patients.

Results

A total of 84/120 enrolled patients met inclusion and diagnostic adjudication criteria. Nineteen percent experiencing the primary outcome had higher STRATIFY scores compared to those event free (233 vs. 212, p = 0.009). Five right heart (TAPSE, TAPSE/PASP, TAPSE/RVDD, RV‐FAC, fwRVLS) and no left heart measures improved prediction (p < 0.05) adjusted for STRATIFY. Right heart measures also had higher variable importance. TAPSE ≥ 17 mm plus STRATIFY improved prediction versus STRATIFY alone (aOR 0.24, 95% confidence interval [CI] 0.06–0.91; NRIcont 0.71, 95% CI 0.22–1.19), and specificity improved by 6%–32% (p < 0.05) at risk thresholds more conservative than the standard‐of‐care benchmark without missing any additional events.

Conclusions

TAPSE increased detection of low‐risk AHF patients, after use of a validated CDI, at risk thresholds more conservative than standard of care.
Anatomical variations of the canine adrenal vessels
Authors: Watanabe Nami , Ono Shin
Published: September 2022

The canine adrenal glands receive blood from the celiac artery, cranial mesenteric artery, caudal phrenic artery, cranial abdominal artery, phrenicoabdominal trunk, abdominal aorta, renal artery and lumbar artery. These are classified into three types: cranial, middle and caudal adrenal branches. It is also known that the adrenal vein flows into the phrenicoabdominal vein. However, individual differences in the branching pattern of adrenal vessels have not been systematically analysed. We evaluated adrenal vessels in dogs that underwent contrast‐enhanced abdominal computed tomography (CT). There were 255 arteries travelling to the adrenal glands in 47 cases, with 1–6 arteries travelling per adrenal gland. The arteries included 67 caudal phrenic arteries, 62 aortic arteries, 60 cranial abdominal arteries, 39 renal arteries, 12 phrenicoabdominal trunks, 8 cranial mesenteric arteries, 6 celiac arteries and 1 lumbar artery. Most of the branches were from the aorta and caudal phrenic artery on the left side, and the cranial abdominal and caudal phrenic artery on the right side. A total of 110 adrenal veins were identified. Inflow into the phrenicoabdominal vein and into the right and left renal veins was observed, and we identified no inflow into other veins. This study demonstrated two points: laterality and individual differences in adrenal blood vessels. When evaluating adrenal blood vessels with abdominal contrast‐enhanced CT, it is recommended to take images under general anaesthesia with breath‐holding and observe them using multiplanar reconstruction.
A core outcome set for pressure ulcers: an important step towards standardized outcome reporting of prevention strategies
Authors: Fledderus Anne C. , Gout H. Antoine
Published: September 2022

Linked Article: Lechner et al. Br J Dermatol 2022; 187:743–752.
Some long-sought answers about vitamin D and keratinocyte carcinoma
Authors: Passarelli Michael N. , Karagas Margaret R.
Published: September 2022

Linked Article:  Ali et al. Br J Dermatol 2022; 187:667–675.
Follicular T helper cells and cutaneous T-cell lymphomas
Authors: Kempf Werner
Published: September 2022

Linked Article:  Wang et al. Br J Dermatol 2022; 187:970–980.
Comprehensive analyses of N6‐methyladenosine‐related long noncoding RNA profiles with prognosis, chemotherapy response, and immune landscape in small cell lung cancer
Authors: Luo Yuejun , Zhang Zhihui , Zheng Bo , Wu Peng , Zhang Guochao , Wang Lide , Zeng Qingpeng , Yang Zhaoyang , Xue Liyan , Zeng Hua , Tan Fengwei , Xue Qi , Gao Shugeng , Sun Nan , He Jie
Published: September 2022

Small cell lung cancer (SCLC) is the most devastating subtype of lung cancer with no clinically available prognostic biomarkers. N6‐methyladenosine (m6A) and noncoding RNAs play critical roles in cancer development and treatment response. However, little is known about m6A‐related long noncoding RNAs (lncRNAs) in SCLC. We used 206 limited‐stage SCLC (LS‐SCLC) samples from two cohorts to undertake the first and most comprehensive exploration of the m6A‐related lncRNA profile in SCLC and constructed a relevant prognostic signature. In total, 289 m6A‐related lncRNAs were screened out. We then built a seven‐lncRNA‐based signature in the training cohort with 48 RNA sequencing data using univariate and multivariate Cox regression models. The signature was well validated in an independent cohort containing 158 cases with quantitative PCR data. In both cohorts, the signature divided patients into high‐ and low‐risk groups with significantly different survival rates (both p < 0.001). Our signature predicted chemotherapy survival benefit in patients with LS‐SCLC. Receiver operating characteristic and C‐index analyses indicated that the signature was better at predicting prognosis and chemotherapy benefit than other clinicopathologic features. Moreover, the signature was identified as an independent predictor of prognosis and chemotherapy response in different cohorts. Furthermore, functional analysis showed that multiple activated immune‐related pathways were enriched in the low‐risk group. Additionally, the signature was also closely related to various immune checkpoints and inflammatory responses. We generated the first clinically available m6A‐related lncRNA signature to predict prognosis and chemotherapy benefit in patients with LS‐SCLC. Our findings could help optimize the clinical management of patients with LS‐SCLC and inform future therapeutic targets for SCLC.
Définir le Musée: Aux Prises avec une Nouvelle Identité
Authors: Nicolas Jérôme , Flieger Katharina
Published: September 2022

Qu’est‐ce qu’un musée ? Le Conseil international des musées (ICOM) l’a défini pour la première fois en 1946 en ces termes : «Le mot “musée” comprend toutes les collections ouvertes au public, de matériel artistique, technique, scientifique, historique ou archéologique, y compris les zoos et les jardins botaniques, mais exclut les bibliothèques, sauf dans la mesure où elles disposent de salles d’exposition permanentes» (ICOM, s.d.).
Luspatercept, a two‐edged sword in beta‐thalassemia‐associated paravertebral extramedullary hematopoietic masses (EHMs)
Authors: Alashkar Ferras , Klump Hannes , Lange Cara Paulina , Proske Pia , Schüssler Maximilian , Yamamoto Raina , Carpinteiro Alexander , Berliner Christoph Alexander , Schlosser Thomas Wilfried , Röth Alexander , Reinhardt Hans Christian
Published: September 2022

Paravertebral extramedullary hematopoietic masses (EHMs) account for up to 15% of extramedullary pseudotumors in beta‐thalassemia (BT) and are most likely related to compensatory hematopoiesis. In most cases, pseudotumors are incidentally detected, as the majority of patients are asymptomatic. Since June 2020, luspatercept is approved for the treatment of patients with BT who require regular red blood cell transfusions. Data addressing the safety and efficacy of luspatercept in patients with BT‐associated EHMs are pending. To date (May 2022), paravertebral EHMs were observed in two asymptomatic patients out of currently 43 adult patients with BT registered at the Adult Hemoglobinopathy Outpatient Unit of the University Hospital Essen, Germany. In one of them, a paravertebral EHM was diagnosed more than 10 years prior to referral. Throughout observation time, treatment with luspatercept was associated with a clinically significant reduction in transfusion burden while allowing to maintain a baseline hemoglobin concentration of ≥10 g/dL aiming to suppress endogenous (ineffective) erythropoiesis associated with BT. Considering the rarity of paravertebral EHMs in BT, luspatercept might potentially represent a novel therapeutic option for these often‐serious disease‐associated complications. However, appropriate follow‐up investigations are recommended to detect (early) treatment failures secondary to an undesired luspatercept‐associated erythroid expansion.
Ibrutinib as a treatment of hematologic autoimmune disorders in patients with indolent B‐cell lymphoma
Authors: Daniel Adrien , Ghez David , Ravaiau Camille , Cavalieri Doriane , Tournilhac Olivier , Herbaux Charles , Roriz Mélanie , Wemeau Mathieu , Guillet Stéphanie , Bossard Jean Baptiste , Hélène Demarquette , Kaphan Eleonore , Caroline Regny , Florence Lachenal , Pierache Adeline , Michel Marc , Godeau Bertrand , Terriou Louis
Published: September 2022

Background

Autoimmune conditions in B‐cell lymphomas are frequent. Steroids are standard of care, but many patients require other immunosuppressive agents. Ibrutinib is a Bruton Tyrosine Kinase inhibitor that is approved for B‐cell indolent lymphoma treatment. We evaluated the use of ibrutinib in previously treated hematologic immune manifestations associated with B‐cell lymphomas.

Results

We conducted a retrospective multicentric observational study. Patients presenting with active, relapsed/refractory B‐cell lymphoma associated hematological immune manifestation (autoimmune cytopenia, acquired immune‐mediated bleeding disorders) were included. Twenty‐five patients were identified. Median age at ibrutinib introduction was 69 years (range 44–84) and median number of previous treatment lines before ibrutinib was 2 (1–7). Twenty‐two patients (88%) were on concomitant stable treatment at inclusion. Within a median exposure of 8 months (2–35), overall response rate to ibrutinib on immune manifestations was 76% (95% CI, 54.9–90.6); complete response rate 44%. Fourteen patients (63%) were able to be weaned from concomitant treatments. Fourteen patients (56%) presented treatment‐related adverse events, mostly Grade 1 or 2.

Conclusions

Ibrutinib in this setting provides good efficacy and safety profile. Clinical trials are needed to define subgroups of patients who will benefit from this strategy and establish its place in the therapeutic arsenal.
Mouse models of Kcnq2 dysfunction
Authors: Brun Lucile , Viemari Jean‐Charles , Villard Laurent
Published: September 2022

Variants in the Kv7.2 channel subunit encoded by the KCNQ2 gene cause epileptic disorders ranging from a benign form with self‐limited epileptic seizures and normal development to severe forms with intractable epileptic seizures and encephalopathy. The biological mechanisms involved in these neurological diseases are still unclear. The disease remains intractable in patients affected by the severe form. Over the past 20 years, KCNQ2 models have been developed to elucidate pathological mechanisms and to identify new therapeutic targets. The diversity of Kcnq2 mouse models has proven invaluable to access neuronal networks and evaluate the associated cognitive deficits. This review summarizes the available models and their contribution to our current understanding of KCNQ2 epileptic disorders.
Towards personalized environment‐aware outdoor gait analysis using a smartphone
Authors: Sher Arshad , Bunker Megan Taylor , Akanyeti Otar
Published: September 2022

Automatic gait analysis in free‐living environments using inertial sensors requires individualized approach as local acceleration and velocity profiles vary with the walker and the topological properties of the environment (e.g., walking in the forest vs. walking on sand). Here, we propose a smartphone‐based gait assessment architecture which consists of two data processing modules. The first module employs a set of personalized classifiers for automatic recognition of the walking environment. The second module provides accurate step time estimates by selecting the optimal filtering frequency tailored to the predicted environment. The performance of the architecture was evaluated using experimental data collected from 10 participants walking in 10 different conditions typically encountered during daily living. Compared with ground truth data, the architecture successfully recognized the walking environments; the percentage of correctly classified instances was above 92%. It also estimated step time with high accuracy; the mean absolute error was less than 10 ms, outperforming or at the very least matching the performance levels achieved in controlled laboratory trials (indoor flat surface walking). Compared with using one filtering frequency for all environments, using optimal frequency tailored to each environment reduced step time estimation error by more than 39%. To the best of our knowledge, this is the first study which successfully demonstrates that parameter tuning can improve gait characterization in outdoor environments. However, further research using a larger data set (including more participants with varying demographics and degree of impairment) is needed to confirm this result. Our findings highlight the importance of environment‐aware gait analysis, and lay the groundwork for a smartphone‐based technology that can be used in the community.
The intramembrane proteases SPPL2a and SPPL2b regulate the homeostasis of selected SNARE proteins
Authors: Ballin Moritz , Griep Wolfram , Patel Mehul , Karl Martin , Mentrup Torben , Rivera‐Monroy Jhon , Foo Brian , Schwappach Blanche , Schröder Bernd
Published: September 2022

Signal peptide peptidase (SPP) and SPP‐like (SPPL) aspartyl intramembrane proteases are known to contribute to sequential processing of type II‐oriented membrane proteins referred to as regulated intramembrane proteolysis. The ER‐resident family members SPP and SPPL2c were shown to also cleave tail‐anchored proteins, including selected SNARE (soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor) proteins facilitating membrane fusion events. Here, we analysed whether the related SPPL2a and SPPL2b proteases, which localise to the endocytic or late secretory pathway, are also able to process SNARE proteins. Therefore, we screened 18 SNARE proteins for cleavage by SPPL2a and SPPL2b based on cellular co‐expression assays, of which the proteins VAMP1, VAMP2, VAMP3 and VAMP4 were processed by SPPL2a/b demonstrating the capability of these two proteases to proteolyse tail‐anchored proteins. Cleavage of the four SNARE proteins was scrutinised at the endogenous level upon SPPL2a/b inhibition in different cell lines as well as by analysing VAMP1‐4 levels in tissues and primary cells of SPPL2a/b double‐deficient (dKO) mice. Loss of SPPL2a/b activity resulted in an accumulation of VAMP1‐4 in a cell type‐ and tissue‐dependent manner, identifying these proteins as SPPL2a/b substrates validated in vivo. Therefore, we propose that SPPL2a/b control cellular levels of VAMP1‐4 by initiating the degradation of these proteins, which might impact cellular trafficking.
Helicobacter pylori infection and risk of multiple sclerosis: An updated meta‐analysis
Authors: Arjmandi Delaram , Abdollahi Ali , Ardekani Ali , Razavian Iman , Razavian Elnaz , Sartip Behnam , Mahjour Sanaz , Parsa Hamid , Kyvanani Nastaran Azizi , Marhoommirzabak Elika , Kountouras Jannis , Rostami Ali
Published: September 2022

Background

There is considerable controversy around the question as to whether Helicobacter pylori (H. pylori) infection has a protective or causative role in the development of multiple sclerosis (MS). This study evaluated published information to assess the association between H. pylori infection and MS.

Methods

We conducted a comprehensive systematic review of relevant observational studies in international databases. A random‐effects model was used to calculate pooled odds ratio (OR) and 95% confidence interval (CI). I2 statistic was used to assess the between‐study heterogeneity. Subgroup and meta‐regression analyses were applied to identify the source of heterogeneity.

Results

In total, 22 studies (25 datasets) were eligible for the meta‐analysis: 17 datasets had prevalence data and eight datasets had data on the mean titer of anti‐H. pylori IgG. The pooled prevalence of H. pylori was 44.1% (908/2606) in the MS patients and 46.1% (1016/2200) in the controls, indicating a non‐significant protective effect of H. pylori on MS (OR, 0.82; 95%CI, 0.58–1.17). In the subgroup analysis, studies that used ELISA yielded a significant protective association (OR, 0.59; 95%CI, 0.46–0.77), while a positive non‐significant association (OR, 1.33; 95%CI, 0.83–2.15) was found from studies that used other serological methods; interestingly, a significant positive association (OR, 6.64; 95%CI, 2.40–13.76) was found from studies that used histological methods to detect H. pylori infection.

Conclusions

Our findings do not support the hypothesis that H. pylori infection represents a protective factor against the development of MS; however, the results varied depending on the diagnostic method(s). Particularly, a significant positive association was identified when studies introduced results based on histological examination, suggesting that active H. pylori infection might be a risk factor for development of MS. Thus, further studies are needed utilizing accurate diagnostic methods to elucidate the association between active H. pylori infection and MS.
Access to information on oral hygiene and mothers' practices of children with microcephaly caused by Zika virus
Authors: Vaz Fernando Flávio Souza , Sobrinho Adriano Referino da Silva , Athayde Fernanda Regina Ribeiro Santos , Carvalho Marianne de Vasconcelos , Sette‐de‐Souza Pedro Henrique , Ferreira Stefânia Jeronimo
Published: September 2022

Objective

To verify whether access to information about oral hygiene influenced the practices of caregivers of children with microcephaly caused by Zika virus (ZIKV).

Methods

A case series study was developed at the Mens Sana Rehabilitation Center, in the municipality of Arcoverde, Pernambuco, Brazil. The study universe included the mothers of 32 children with microcephaly caused by Zika virus. Data collection took place in June 2018 and was carried out through a structured questionnaire. The variables studied comprised socioeconomic issues, habits, diet, and knowledge about oral hygiene. Fisher's Exact and Pearson's Chi‐square tests were used with a significance level of 5%.

Results

Out of 32 individuals eligible to participate in the study, only 27 were selected. Most mothers reported receiving information about oral hygiene from their infants (63.0%). Fisher's Exact and Pearson's Chi‐square tests showed that access to oral hygiene information was associated with mother's education, family income, regular visits to the dentist, frequency of tooth brushing, age at which the infant started brushing, and brushing time (p < 0.05).

Conclusion

Access to information about oral hygiene positively influenced the oral health care of mothers with their children with microcephaly caused by ZIKV.
Impact of serum vitamin D levels on periodontal healing outcomes: A preliminary cohort study
Authors: Ribeiro Lívia Silva Figueiredo e , Araujo Nara Santos , Zilli Vieira Carolina Letícia , dos Santos Jean Nunes , Cury Patricia Ramos
Published: September 2022

Objective

To evaluated the relationship between serum vitamin D levels and periodontal healing outcomes in patients with mild or moderate periodontitis.

Methods

Serum vitamin D levels and periodontal pockets and gingival bleeding were evaluated in 51 patients before and 6 months after non‐surgical periodontal treatment. At‐test and chi‐square test were used to analyse the data (p ≤ 0.05).

Results

The mean reduction of periodontal pocket depth was statistically significant higher in patients with vitamin D ≥30 ng/ml than those with <30 ng/ml (CI = −0.23–0.42,p = 0.05), but not clinically significant. Vitamin D level was not associated with the percentage of sites of gingival bleeding on probing at the final evaluation (OR = 0.58, 95% CI = 0.17–1.99,p = 0.39).

Conclusion

Lower serum vitamin D level was associated with a slightly reduced periodontal healing after non‐surgical periodontal therapy, which should be further investigated in a larger population.
IRREVERSIBILITY AND MONITORING IN DYNAMIC GAMES: EXPERIMENTAL EVIDENCE
Authors: Lee Eungik , Choi Andrew , Choi Syngjoo , Guéron Yves
Published: September 2022

This article provides experimental evidence on the impacts of irreversibility and imperfect monitoring on the efficiency and the equity of a repeated public goods game. We find that irreversibility and imperfect monitoring both lead to inefficient and unequal outcomes through different channels. Irreversibility lowers public goods contribution in earlier periods and makes the initial‐period contribution gap between two players long‐lasting. Imperfect monitoring hampers conditional cooperation and persistently reduces group contribution. A finite mixture estimation with conditional cooperators provides a coherent account of the treatment effects.
Fast‐flowing LBE corrosion of the SiC pump impeller: Numerical and experimental investigations
Authors: Li Xianhui , Zeng Xian , Zhao Zhanchong , Zhang Xiaoxin , Yan Qingzhi , Zhang Youyuan , Wen Yuying , Yang Xuanbing , Mao Feng
Published: September 2022

In order to determine the stress state and the specific dynamic corrosion behaviors of the cooling pump impeller in the liquid lead‐bismuth eutectic alloy (LBE), the numerical and the experimental investigations on the fast‐flowing LBE corrosion behaviors of the SiC impeller were conducted. The distributions of stress and displacement of the SiC impeller were simulated, and then the microstructure and mechanical properties of the corroded impeller were characterized. The results indicated that the SiC impeller met the strength requirement of 1000 rpm in LBE, and the dynamic LBE corrosion had little effect upon structure safety of the SiC impeller. The maximum stresses of the SiC impeller without and with LBE loading were .452 and 9.736 MPa, respectively. The maximum displacements of the SiC impeller without and with LBE loading were 76.385 and 4.096 μm, respectively. The LBE loading reduced the axial displacement of the impeller and acted as an impeller stabilizer to some extent. Blade elongating and flapping were the main vibration mode of the SiC impeller. The mechanical properties of the SiC impellers before and after corrosion were basically the same.
The Boston ASL Template and Simulator: Initial development and implementation
Authors: Taso Manuel , Munsch Fanny , Alsop David C.
Published: September 2022

Background and purpose

Templates are a hallmark of image analysis in neuroimaging. However, while numerous structural templates exist and have facilitated single‐subject and large group studies, templates based on functional contrasts, such as arterial spin labeling (ASL) perfusion, are scarce, have an inherently low spatial resolution, and are not as widely distributed. Having such tools at one's disposal is desirable, for example, in the case of studies not acquiring structural scans. We here propose an initial development of an ASL adult template based on high‐resolution fast spin echo acquisitions.

Methods

High‐resolution single‐delay ASL, low‐resolution multi‐delay ASL, T1‐weighted magnetization prepared rapid acquisition 2 gradient echoes, and T2 fluid attenuated inversion recovery data were acquired in a cohort of 10 healthy volunteers (6 males and 4 females, 30± 7 years old). After offline reconstruction of high‐resolution perfusion arterial transit time (ATT) and T1 maps, we built a multi‐contrast template relying on the Advanced Normalization Toolbox multivariate template nonlinear construction framework. We offer examples for the registration of ASL data acquired with different sequences. Finally, we propose an ASL simulator based on our templates and a standard kinetic model that allows generating synthetic ASL contrasts based on user‐specified parameters.

Results

Boston ASL Template and Simulator (BATS) offers high‐quality, high‐resolution perfusion‐weighted and quantitative perfusion templates accompanied by ATT and different anatomical contrasts readily available in the Montreal Neurological Institute space. In addition, examples of use for data registration and as a synthetic contrast generator show various applications in which BATS could be used.

Conclusions

We propose a new ASL template collection, named BATS, that also includes a simulator allowing the generation of synthetic ASL contrasts. BATS is available at http://github.com/manueltaso/batsasltemplate.
The empathic personality profile: Using personality characteristics to reveal genetic, environmental, and developmental patterns of adolescents' empathy
Authors: Abramson Lior , Eldar Eran , Markovitch Noam , Knafo‐Noam Ariel
Published: September 2022

Objective

How do genetic and environmental processes affect empathy during early adolescence? This study illuminated this question by examining the aetiology of empathy with the aetiology of other personality characteristics.

Method

Israeli twin adolescents rated their empathy and personality at ages 11 (N = 1176) and 13 (N = 821) (733 families, 51.4% females). Parents rated adolescents' emotional empathy. Adolescents performed an emotion recognition task, indicating cognitive empathy.

Results

Using a cross‐validated statistical learning algorithm, this study found emotional and cognitive “empathic personality profiles,” which describe and predict self‐reported empathy from nuanced Big‐Five personality characteristics, or “nuances” (i.e., individual items). These profiles predicted empathy moderately (R2 = 0.17–0.24) and were stable and robust, within each age and between ages. They also predicted empathy in a new sample of older nontwin adolescents (N = 96) and were validated against non‐self‐report empathy measures. Both emotional and cognitive empathy were predicted by nuances representing positive attitudes toward others, trust, forgiveness, and openness to experiences. Emotional empathy was also predicted by nuances representing anxiousness and negative reactivity. Twin analyses revealed overlapping genetic and environmental influences on empathy and the empathic personality profiles and overlapping environmental influences on empathy–personality change.

Conclusions

This study demonstrates how addressing the complexity of individuals' personalities can inform adolescents' empathy development.
Neopestalotiopsis longiappendiculata as the agent of grey blight disease of Camellia spp.
Authors: Wang Qiu‐Tong , Cheng Yuan‐Hui , Zhuo Lan , Wang Yu , Zhou Hao , Hou Cheng‐Lin
Published: September 2022

The grey blight disease is a common disease of tea plants and camellias (Camellia spp.). It is caused by Pestalotiopsis‐like fungi, which were mostly identified as species of Pestalotiopsis and Pseudopestalotiopsis. In this study, four strains of Neopestalotiopsis were isolated from brown and grey‐white spots of leaves of Camellia oleifera and C. sasanqua in China. These strains belong to Neopestalotiopsis longiappendiculata and are characterized by morphology and multi‐loci phylogenetic analysis (ITS‐tef‐tub2). This is the first report of N. longiappendiculata as agent of grey blight disease on Camellia spp. Pathogenicity tests indicated that N. longiappendiculata infects not only Camellia oleifera and Camellia sasanqua but also Eucalyptus polyanthemos and Euonymus japonicas. Given the broad host range and pathogenic nature, it is time to focus on management aspect to control the disease.