bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental dynamics of the postsynaptic proteome to understand synaptic maturation and dysmaturation
Authors: Kaizuka Takeshi , Suzuki Takehiro , Kishi Noriyuki , Kilimann Manfred W. , Ueyama Takehiko , Watanabe Masahiko , Okano Hideyuki , Dohmae Naoshi , Takumi Toru
Published: May 2022

The postsynaptic density (PSD) is a protein condensate composed of ∼1,000 proteins beneath the postsynaptic membrane of excitatory synapses. The number, shape, and plasticity of synapses are altered during development. However, the dynamics of synaptic protein composition across development have not been fully understood. Here we show alterations of PSD protein composition in mouse and primate brains during development. Proteins involved in synapse regulation are enriched in the differentially expressed (288 decreased and 267 increased) proteins on mouse PSD after a 2-week-old. We find that the changes in PSD protein abundance in mouse brains correlate with gene expression levels in postnatal mice and perinatal primates. This alteration of PSD composition is likely to be defective in the brains of mouse models or patients with autism spectrum disorder (ASD). Finally, we demonstrate that the brain of the common marmoset (Callithrix jacchus) changes PSD composition after the juvenile period. The alteration of PSD composition after 2-month-old is distinct from that observed in mice. Our results provide a comprehensive architecture of the remodeling of PSD composition across development, which may explain the molecular basics of synapse maturation and the pathology of psychiatric disorders, such as ASD.
Multiple instance learning to predict immune checkpoint blockade efficacy using neoantigen candidates
Authors: Lang Franziska , Sorn Patrick , Schrörs Barbara , Weber David , Kramer Stefan , Sahin Ugur , Löwer Martin
Published: May 2022

A successful response to immune checkpoint blockade treatment (ICB) depends on the functional re-invigoration of neoantigen-specific T cells and their anti-tumoral activity. Previous studies showed that the patient’s neoantigen candidate load is an imperfect predictor of the response to ICB. Further studies provided evidence that the overall response to ICB is also affected by the qualitative properties of a few or even single candidates, limiting the predictive power based on candidate quantity alone.

To our knowledge, this is the first study to predict the response to ICB therapy based on qualitative neoantigen candidate profiles in the context of the mutation type, using a multiple instance learning approach. Multiple instance learning is a special branch of machine learning which classifies labelled bags that are formed by a set of unlabeled instances. The multiple instance learning approach performed systematically better than random guessing and was independent of the neoantigen candidate load. Qualitative modeling performed better in comparison to the quantitative approach, in particular for modelling low-abundant fusion genes. Our findings suggest that multiple instance learning is an appropriate method to predict immunotherapy efficacy based on qualitative neoantigen candidate profiles without relying on direct T-cell response information and provide a foundation for future developments in the field.
Suppression of tumor/host intrinsic CMTM6 drives anti-tumor cytotoxicity in a PD-L1 independent manner
Authors: Long Yiru , Chen Runqiu , Yu Xiaolu , Tong Yongliang , Peng Xionghua , Li Fanglin , Hu Chao , Sun Jianhua , Gong Likun
Published: May 2022

CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6) has been identified as a regulator of membranal programmed death ligand 1 (PD-L1) stability and a factor associated with malignancy progression, but the effects and mechanisms of CMTM6 on tumor growth, as well as its potential for therapy, are still largely unknown. Here, we show that tumor CMTM6 increased with progression in both clinical patients and mice. Ablation of CMTM6 resulted in significant retardation of human and murine tumor growth dependent on T-lymphocyte immunity. Tumor CMTM6 suppression broke resistance to immune checkpoint inhibitors and remodeled the tumor immune microenvironment, as specific antitumor cytotoxicity was enhanced and contributed primarily to tumor inhibition. Further, without the PD-1/PD-L1 axis, CMTM6 suppression still significantly dampened tumor growth dependent on cytotoxic cells. Notably, we identified that CMTM6 was widely expressed on immune cells. T-cell CMTM6 increased with sustained immune activation and intratumoral immune exhaustion and affected the T-cell-intrinsic PD-L1 levels. Host CMTM6 knockout significantly restrained tumor growth dependent on CD8+ T-cells, and similarly, not entirely dependent on PD-L1. Thus, we developed and evaluated the antitumor efficacy of CMTM6-targeting adeno-associated virus (AAV), which effectively mobilized antitumor immunity and could be combined with various antitumor drugs. Our findings reveal that both tumor and host CMTM6 are deeply involved in tumor immunity with or without the PD-1/PD-L1 axis and that gene therapy targeting CMTM6 is a promising strategy for cancer immunotherapy.

One Sentence Summary

Even in the absence of the PD-1/PD-L1 axis, tumor or host CMTM6 deficiency can mediate cytotoxicity-dependent anti-tumor immune responses, allowing CMTM6 to be a novel target for scAAV-mediated oncoimmunology gene therapy and combination treatment.
Piezo buffers mechanical stress via modulation of intracellular Ca2+ handling in the Drosophila heart
Authors: Zechini Luigi , Camilleri-Brennan Julian , Walsh Jonathan , Beaven Robin , Moran Oscar , Hartley Paul S. , Diaz Mary , Denholm Barry
Published: May 2022

Throughout its lifetime the heart is buffeted continuously by dynamic mechanical forces resulting from contraction of the heart muscle itself and fluctuations in haemodynamic load and pressure. These forces are in flux on a beat-by-beat basis, resulting from changes in posture, physical activity or emotional state, and over longer timescales due to altered physiology (e.g. pregnancy) or as a consequence of ageing or disease (e.g. hypertension). It has been known for over a century of the heart’s ability to sense differences in haemodynamic load and adjust contractile force accordingly1-4. These adaptive behaviours are important for cardiovascular homeostasis, but the mechanism(s) underpinning them are incompletely understood. Here we present evidence that the mechanically-activated ion channel, Piezo, is an important component of the Drosophila heart’s ability to adapt to mechanical force. We find Piezo is a sarcoplasmic reticulum (SR)-resident channel and is part of a mechanism that regulates Ca2+ handling in cardiomyocytes in response to mechanical stress. Our data support a simple model in which Drosophila Piezo transduces mechanical force such as stretch into a Ca2+ signal, originating from the SR, that modulates cardiomyocyte contraction. We show that Piezo mutant hearts fail to buffer mechanical stress, have altered Ca2+ handling, become prone to arrhythmias and undergo pathological remodelling.
Understanding the role of c-di-AMP signaling in determining antibiotic tolerance in Mycobacterium smegmatis: generation of resistant mutants and regrowth of persisters
Authors: Pal Aditya Kumar , Ghosh Anirban
Published: May 2022

In this study, we probe the role of secondary messenger c-di-AMP in drug tolerance, which includes both persister and resistant mutant characterization of Mycobacterium smegmatis. Specifically, with the use of c-di-AMP null and overproducing mutants, we showed how c-di-AMP plays a significant role in resistance mutagenesis against antibiotics with different mechanisms of action. We elucidated the specific molecular mechanism linking the elevated intracellular c-di-AMP level and high mutant generation and highlighted the significance of non-homology-based DNA repair. Further investigation enabled us to identify the unique mutational landscape of target and non-target mutation categories linked to intracellular c-di-AMP levels. Overall fitness cost of unique target mutations was estimated in different strain backgrounds, and then we showed the critical role of c-di-AMP in driving epistatic interactions between resistance genes, resulting in the evolution of multi-drug tolerance. Finally, we identified the role of c-di-AMP in persister cells regrowth and mutant enrichment upon cessation of antibiotic treatment.
Insulin Receptor Loss Impairs Mammary Tumorigenesis in Mice
Authors: Podmore Lauren , Poloz Yekaterina , Iorio Catherine , Mouaaz Samar , Nixon Kevin , Smirnov Petr , McDonnell Brianna , Lam Sonya , Zhang Bowen , Tharmapalan Pirashaanthy , Sarkar Soumili , Vyas Foram , Ennis Marguerite , Dowling Ryan , Stambolic Vuk
Published: May 2022

Breast cancer (BC) prognosis and outcome are adversely affected by obesity. Hyperinsulinemia, common in obese state, is associated with higher risk of death and recurrence in BC. Up to 80% of breast cancers overexpress the insulin receptor (INSR), which correlates with worse prognosis. INSR role in mammary tumorigenesis was tested by generating MMTV-driven polyoma middle T (PyMT) and ErbB2/Her2 BC mouse models, respectively, with coordinate mammary epithelium-restricted deletion ofINSR. In both models, deletion of either one or both copies ofINSRled to a marked delay in tumor onset and burden. Longitudinal phenotypic characterization of mouse tumours and cells revealed that INSR deletion impacted tumour initiation, not progression and metastasis. INSR upheld a bioenergetic phenotype in non-transformed mammary epithelial cells, independent of its kinase activity. Similarity of phenotypes elicited by deletion of one or both copies ofINSRsuggest a dose-dependent threshold for INSR impact on mammary tumorigenesis.
Isolation and structural comparison of RuII-dnp complexes [dnp = 2,6-bis(1,8-naphthyridin-2-yl)pyridine] with axially or equatorially coordinating NCS ligands
Authors: Takase Tsugiko , Yamanaka Takashi , Tamura Chihiro , Oyama Dai
Published: May 2022

The molecular and crystal structures of two ruthenium(II) complexes, viz. cis-aqua[2,6-bis(1,8-naphthyridin-2-yl)pyridine-κ3
N,N′,N′′](thiocyanato-κN)(triphenylphosphine-κP)ruthenium(II) hexafluoridophosphate–acetone–water (1/0.5/1), [Ru(NCS)(C21H13N5)(C18H15P)(H2O)]PF6·0.5C3H6O·H2O (I) and trans-[2,6-bis(1,8-naphthyridin-2-yl)pyridine-κ3'N,N′,N′′]bis(pyridine-κN)(thiocyanato-κN)ruthenium(II) thiocyanate, [Ru(NCS)(C21H13N5)(C5H5N)2]NCS (II), with an N-coordinating thiocyanato group and a tridentate polypyridyl supporting ligand, are reported. The RuII atom in each of the cationic complexes adopts a distorted octahedral coordination sphere, defined by an N atom of the thiocyanato ligand, three N atoms from the tridentate polypyridyl ligand, and an O and P atom in (I) or two pyridine-N atoms in (II) derived from monodentate ligands. The thiocyanato ligand in (I) coordinates in an axial manner to the {Ru-dnp} unit [dnp = 2,6-bis(1,8-naphthyridin-2-yl)pyridine], whereas it coordinates in an equatorial manner in (II). In the crystal structure of compound (I), intramolecular C—H...O, C—H...N and O—H...N hydrogen bonds as well as π–π contacts are present, in addition to intermolecular C—H...F, C—H...O and O—H...O hydrogen bonds. In the crystal structure of compound (II), intramolecular C—H...N hydrogen bonds are observed along with intermolecular C—H...N and C—H...S hydrogen bonds as well as a π–π interaction.
Modelling searching on academic social networking sites: a focus on learning outcomes
Authors: Wu Dan , Lu Liuxing , Cheng Lei
Published: May 2022

Purpose

This paper aims to establish a theoretical search model on academic social networking sites (ASNSs).

Design/methodology/approach

Based on the characteristics of ASNSs and a previous extended sense-making model, this paper first presented an initial model of searching on ASNSs. Next, an online survey was conducted on ResearchGate to understand the search processes and outcomes with the help of a survey questionnaire. In total, 359 participants from 70 countries participated in this online survey. The survey results provided a basis for modifying the initial model.

Findings

Results showed that the theoretical model of searching on ASNSs included motives for searching on ASNSs, identification of needs, search triggered by information needs, search triggered by social needs and outcomes. The search triggered by information needs was significantly positively correlated with learning outcomes. Besides learning outcomes, searching on ASNSs could help user amplify their social networks and promote research dissemination.

Practical implications

Understanding users’ search habits and knowledge acquisition can provide insights for ASNSs to design an interface to support searching and enhance learning. Moreover, the proposed model can help users recognize their knowledge status and learning effects and improve their learning efficiency.

Originality/value

This paper contributes to establishing a theoretical model to understand users’ search process and outcomes on ASNSs.
“Konnichiwa, Mr. Robot”: a direct observation of hotel visitors' attitudes and anxiety regarding service robots
Authors: Leung Rosanna
Published: May 2022

Purpose

This study investigates human behavior, specifically attitude and anxiety, toward humanoid service robots in a hotel business environment.

Design/methodology/approach

The researcher adopted direct observations and interviews to complete the study. Visitors of Henn-na Hotel were observed and their spatial distance from the robots, along with verbal and non-verbal behavior, was recorded. The researcher then invited the observed hotel guests to participate in a short interview.

Findings

Most visitors showed a positive attitude towards the robot. More than half of the visitors offered compliments when they first saw the robot receptionists although they hesitated and maintained a distance from them. Hotel guests were also disappointed with the low human–robot interaction (HRI). As the role of robots in hotels currently remains at the presentation level, a comprehensive assessment of their interactive ability is lacking.

Research limitations/implications

This study contributes to the HRI theory by confirming that people may treat robots as human strangers when they first see them. When a robot's face is more realistic, people expect it to behave like an actual human being. However, as the sample size of this study was small and all visitors were Asian, the researcher cannot generalize the results to the wider population.

Practical implications

Current robot receptionist has limited interaction ability. Hotel practitioners could learn about hotel guests' behavior and expectation towards android robots to enhance satisfaction and reduce disappointment.

Originality/value

Prior robot research has used questionnaires to investigate perceptions and usage intention, but this study collected on-site data and directly observed people's attitude toward robot staff in an actual business environment.
Corporate narrative reporting on Industry 4.0 technologies: does governance matter?
Authors: Hussainey Khaled , Albitar Khaldoon , Alkaraan Fadi
Published: May 2022

Purpose

This paper aims to provide early evidence on corporate transformation towards Industry 4.0 (CTTI4) in the UK, particularly by examining the effect of corporate governance on the narrative reporting of CTTI4.

Design/methodology/approach

The authors analyse all UK financial times stock exchange all-share non-financial firms that have published their annual reports for the period of 2013–2018. The authors use computerised textual analysis to measure the level of corporate reporting on Industry 4.0 (I4.0) for 1,001 firm-year observations. The authors used different regression models to test the research hypotheses.

Findings

The findings contribute to the growing literature on business model transformation in UK companies towards the I4.0 strategy. The findings show that the level of reporting on CTTI4 is improving over the sample period and varies between industries. The authors also find that better governance quality enhances the level of reporting on CTTI4.

Practical implications

The findings of this study inform decision makers and regulators about factors driving UK companies to report information about their actionable strategies to direct I4.0 endeavours.

Originality/value

The paper makes an important and novel contribution to corporate disclosure literature. So far as the authors know, it is the only paper to examine the impact of corporate governance on corporate narrative reporting on I4.0 technologies. Moreover, to the best of the authors’ knowledge, it is the first paper to show that the quality of corporate governance adds value to this strategic type of corporate disclosure.
The impact of supply chain relationship configurations on supplier performance: investigating buyer–supplier relations in the aerospace industry
Authors: Schmelzle Ulrich , Mukandwal Prabhjot S.
Published: May 2022

Purpose

A supplier may sell not only to one buyer (sole relationship configuration) but also to the buyers competitors (shared relationship configuration) for a specific product category. This study examines the performance implications when suppliers establish shared relationships with the buyer’s competitors.

Design/methodology/approach

Secondary data are used to test hypotheses relating a supplier’s relationship configurations to its operational performance. A seemingly unrelated regression approach (SUR) is applied to analyze the data, followed by endogeneity checks of the empirical findings.

Findings

The study shows that suppliers with less-shared ties with buying firms’ competitors exhibit superior inventory efficiency and asset turnover. Thus, suppliers can improve operational efficiency by creating relatively exclusive, deep and trust-based relations instead of more extensively shared and shallower relationships.

Research limitations/implications

Based on agency theory as a theoretical lens and aerospace industry data, this research contributes by addressing the supplier’s perspective and linking its operational efficiency performance with its chosen supply relationship configuration.

Practical implications

Suppliers need to understand the performance implications of choosing relatively exclusive relationships versus shared relationships with buying firms. The research provides new insights for managers and can guide their supply chain decision-making.

Originality/value

Little is known about how a supplier’s relationship configurations can elevate, or impair, its operational efficiency. While conventional wisdom holds that suppliers should focus on multiple avenues of revenue growth by selling to buyers’ competitors, this study demonstrates that more sales to a buying firm’s rivals might, in fact, reduce a supplier’s efficiency.
The development of the Chinese wine industry and trade
Authors: Mizik Tamás , Balogh Jeremiás Máté
Published: May 2022

Purpose

The study aims to give an overview of the development of the Chinese wine industry and trade between 1992 and 2019. Its importance is highlighted by the fact that China has become one of the world’s largest wine-consuming markets with great growth potential and is now ranked among the top 10 largest global markets for wine.

Design/methodology/approach

To address Chinese wine industry competitiveness, revealed comparative advantage (RCA), relative trade advantage (RTA) and revealed competitiveness (RC) were calculated, based on the World Bank World Integrated Trade Solution database. Chinese wine market-related issues are analyzed by Porter’s Five Forces in help of Market Line industry profile reports.

Findings

Results suggest that the Chinese wine market is relatively fragmented, with a concentrated food and beverages retail industry, strong buyer power and a moderate supplier power. The RCA calculated for the Chinese wine trade indicates that the share of exported bottled wine has become significant in the analyzed period. However, the RCA was perceivable just for bottled wines and only in the last analyzed period (2013–2019), whereas RTA and RC were negative for all periods revealing a comparative disadvantage. However, current market trends suggest that they will increase in the future.

Research limitations/implications

Data accuracy may affect these results because wine statistics may contain mislabeling. Moreover, China expanded its investments in many well-known wine regions all over the world, especially in Bordeaux, France. These, along with the significant re-export, could make it harder to interpret wine trade data because some part of the export is related to Chinese wineries outside of China.

Practical implications

Knowing the above-mentioned limitations, results should be interpreted with caution. However, high-quality wines can be identified as a niche market in China.

Originality/value

The study provided a detailed analysis of the Chinese wine industry and its competitiveness.
The impact of COVID-19 on conventional and Islamic stocks: empirical evidence from Pakistan
Authors: Bhutto Niaz Ahmed , Khan Shabeer , Khan Uzair Abdullah , Matlani Anjlee
Published: May 2022

Purpose

The purpose of this study is to investigate the impact of COVID-19 on conventional and Islamic stocks by using the data spanning from February 25, 2020, to February 3, 2021, and employing a panel regression approach.

Design/methodology/approach

In this study a panel regression approach has been used.

Findings

The study finds a negative association between COVID-19 and stock (both Islamic and conventional). After splitting the data into 1st and 2nd waves, the relationship between COVID-19 and stock (both Islamic and conventional) remains the same (negative) in the case of the 1st wave. In contrast, in the case of the 2nd wave, the relationship turned out to be positive. During both waves of the pandemic, the magnitude of the effect is found to be higher for conventional stocks. Additionally, the study also analyzes the aggregate influence of COVID-19 on different sectors and finds that commercial banks, oil and gas exploration and marketing companies are the most influenced sectors. At the same time, automobiles and pharma are the least affected sectors.

Practical implications

The study suggests that markets start gaining momentum to reach their prepandemic level after absorbing the initial shock (emergence of a pandemic). The study also provides thorough insights for market regulators and policymakers by implying the dynamic relations between markets (conventional and Islamic) and financial crisis, which would allow them more effective control of crisis in future endeavors.

Originality/value

This is one of the first studies to investigate the impact of COVID-19 on both conventional and Islamic stocks, especially in the context of Pakistan.
CEO polychronicity and SME internationalization
Authors: Agnihotri Arpita , Bhattacharya Saurabh
Published: May 2022

Purpose

This study, leveraging the upper echelon and social network theories, aims to explore the association between chief executive officers (CEO’s) polychronicity and small and medium size enterprises (SMEs’) international performance under the complete mediation effect of social networks. The paper explores this relationship under the moderation effect of CEO perceived time pressure and synchrony preference.

Design/methodology/approach

The paper investigates a moderated mediating relationship based on a sample of 186 UK firms.

Findings

The findings of this study suggest that social network fully mediates the CEO polychronicity and firm international performance relationship. Furthermore, CEO perceived time pressure moderates the social network and SME international performance relationship such that it reduces the positive indirect association between CEO polychronicity and SME international performance. CEO synchrony preference, on the contrary, enhances the positive indirect association between CEO polychronicity and SME performance.

Originality/value

Extant research suggests SMEs having a more robust set of organizational capabilities helps them network and avail foreign market knowledge. However, research exploring antecedents of this organizational capability is scant.
Feedbacks between size and density determine rapid eco‐phenotypic dynamics
Authors: Gibert Jean P. , Han Ze‐Yi , Wieczynski Daniel J. , Votzke Samantha , Yammine Andrea
Published: May 2022

Body size is a fundamental trait linked to many ecological processes—from individuals to ecosystems. Although the effects of body size on metabolism are well‐known, the potential reciprocal effects of body size and density are less clear. Specifically, (a) whether changes in body size or density more strongly influence the other and (b) whether coupled rapid changes in body size and density are due to plasticity, rapid evolutionary change or a combination of both.

Here, we address these two issues by experimentally tracking population density and mean body size in the protistTetrahymena pyriformisas it grows from low density to carrying capacity. We then use Convergent Cross Mapping time series analyses to infer the direction, magnitude and causality of the link between body size and population dynamics. We confirm the results of our analysis by experimentally manipulating body size and density while keeping the other constant. Last, we fit mathematical models to our experimental time series that account for purely plastic change in body size, rapid evolution in size, or a combination of both, to gain insights into the processes that most likely explain the observed dynamics.

Our results indicate that changes in body size more strongly influence changes in density than the other way around, but also show that there is reciprocity in this effect (i.e., a feedback). We show that a model that only accounts for purely plastic change in size most parsimoniously explains observed, coupled phenotypic and ecological dynamics.

Together, these results suggest (a) that body size can shift dramatically through plasticity, well within ecological timescales, (b) that rapid changes in body size may have a larger effect on population dynamics than the reverse, but (c) phenotypic and population dynamics influence each other as populations grow. Overall, we show that rapid plastic changes in functional traits like body size may play a fundamental—but currently unrecognized—role in familiar ecological processes such as logistic population growth.

Read the freePlain Language Summaryfor this article on the Journal blog.
Stopping nucleot(s)ide analogues in non‐cirrhotic HBeAg‐negative chronic hepatitis B patients: HBsAg loss at 96 weeks is associated with low baseline HBsAg levels
Authors: Hall Samuel A. L. , Burns Gareth S. , Anagnostou Despina , Vogrin Sara , Sundararajan Vijaya , Ratnam Dilip , Levy Miriam T. , Lubel John S. , Nicoll Amanda J. , Strasser Simone I. , Sievert William , Desmond Paul V. , Ngu Meng C. , Angus Peter , Sinclair Marie , Meredith Christopher , Matthews Gail , Revill Peter A. , Jackson Kathy , Littlejohn Margaret , Bowden D. Scott , Locarnini Stephen A. , Visvanathan Kumar , Thompson Alexander J.
Published: May 2022

Background and Aims

Current guidelines recommend long‐term nucleot(s)ide analogue (NA) therapy for patients with HBeAg‐negative chronic hepatitis B (CHB). However, disease remission has been described after stopping NA therapy, as well as HBsAg loss.

Methods

We performed a prospective multi‐centre cohort study of stopping NA therapy. Inclusion criteria were HBeAg‐negative CHB, the absence of cirrhosis and HBVDNA<lower limit of quantification for ≥18 months. We assessed virological and biochemical outcomes including HBsAg loss, as well as NA restart rates, over 96 weeks.

Results

In total, 110 patients [62% entecavir (ETV); 28% tenofovir (TDF), 10% other] were enrolled. Median age was 56 years, 57% were male, 85% were Asian, median baseline HBsAg level was 705 (214–2325) IU/ml. Virological reactivation occurred in 109/110 patients, median time to detection was 8 (4–12) weeks, and occurred earlier after stopping TDF versus ETV (median 4 vs. 12 weeks p < 0.001). At week 96, 77 (70%) remained off‐treatment, 65 (59%) had ALT <2× ULN, 31 (28%) patients were in disease remission with HBVDNA <2000 IU/ml plus ALT <2× ULN and 7 (6%) patients had lost HBsAg. Baseline HBsAg ≤10 IU/ml was associated with HBsAg loss (6/9 vs. 1/101 p < 0.001). ALT >5× ULN occurred in 35 (32%); ALT flares were not associated with HBsAg loss. There were no unexpected safety issues.

Conclusion

Virological reactivation was very common after stopping NA therapy and occurred earlier after stopping TDF versus ETV. The majority of patients had ALT <2× ULN at week 96, but only one‐third achieved disease remission and HBsAg loss was rare. Very low HBsAg levels at baseline were uncommon but predicted for HBsAg loss and disease remission.
Pharmacogenetic predictors of variability in efavirenz pharmacokinetics in an admixed Brazilian HIV cohort
Authors: Ximenez João Paulo , Elias Anna Beatriz Ribeiro , Nardotto Glauco Henrique Balthazar , Barroso Paulo Feijó , Bollela Valdes Roberto , Lanchote Vera Lucia , Suarez‐Kurtz Guilherme
Published: May 2022

Aims

To investigate the influence of pharmacogenetic polymorphisms on efavirenz (EFV) exposure and metabolism in HIV‐infected Brazilians under treatment with EFV‐containing antiretroviral (ART) regimens.

Methods

HIV‐positive adults (n = 82) on stable ART regimens containing 600 mg EFV once daily for at least 6 months were recruited at 2 university hospitals. Blood samples collected at mid‐dose interval were used to quantify the plasma concentrations of EFV (denoted [EFV]), its major metabolite 8‐OH‐EFV ([8‐OH‐EFV]) and [8‐OH‐EFV]/[EFV] metabolic ratio, and to genotype single nucleotide polymorphisms in CYP2B6 (rs3745274, c.516G > T; rs28399499, c.983 T > C) and ABCB1 (rs3842, c.4036G > A). CYP2B6 metabolic phenotypes were inferred from the CYP2B6 diplotypes. Linear regression modelling was applied to identify sociodemographic, clinical and pharmacogenetic predictors of [EFV] and [8‐OH‐EFV]/[EFV] metabolic ratio.

Results

Wide (50‐fold) interindividual variation in [EFV], [8‐OH‐EFV] and [8‐OH‐EFV]/[EFV] was observed; 69.5% of participants had [EFV] within the nominal therapeutic range (1000–4000 ng/mL), while 19.5 and 11.0% had [EFV] below and above this range, respectively. Multiple regression modelling retained only CYP2B6 metabolic phenotypes or the combined rs3745274 and rs28399499 genotypes, as significant predictors of [EFV] and [8‐OH‐EFV]/[EFV].

Conclusion

EFV exposure and disposition varied widely among HIV‐infected Brazilians under stable treatment with EFV‐containing ART regimens. About 1/10 of the participants had [EFV] exceeding nominal supratherapeutic concentration (4000 ng/mL), but reported tolerance to the ARV regimens, while 1/5 of participants had nominal subtherapeutic [EFV] (<1000 ng/mL) but adequate virological response. Genotype for the 2 CYP2B6 single nucleotide polymorphisms studied explained 48% of variation in [EFV] and 35% of variation in [8‐OH‐EFV]/[EFV].
From pity to numbness: Social exclusion moderates the relationship between trait empathy and bystanders’ aggressive tendencies in cyberbullying
Authors: Gao Lu , Liu Cheng‐Hong , Yin Xian‐Rui
Published: May 2022

Studies on cyberbullying have revealed an inconsistent relationship between trait empathy and bystanders’ aggressive tendencies towards victims. We believe that these studies have overlooked the role of social exclusion. We infer that high‐severity social exclusion suppresses the negative relationship between trait empathy and bystanders’ aggressive tendencies. In Study 1, 226 participants read a news report concerning a singer's humiliation by netizens due to lack of talent. The results revealed that trait empathy predicted lower aggressive tendencies towards the singer for participants with fewer experiences of social exclusion. However, trait empathy was unrelated to aggressive tendencies for participants with more experiences of social exclusion. In Study 2, 146 participants were randomly assigned to a low‐severity or a high‐severity social exclusion condition and were required to recall their experiences of low‐ or high‐severity social exclusion, respectively. The results demonstrated that in the low‐severity condition, trait empathy was negatively associated with participants’ aggressive tendencies towards the singer and this relationship was mediated by state empathy. However, there was no evidence that the process was at work in the high‐severity condition. This study further presents implications and directions for future research.
Optimal Allocation of Finite Sampling Capacity in Accumulator Models of Multialternative Decision Making
Authors: Ramírez‐Ruiz Jorge , Moreno‐Bote Rubén
Published: May 2022

When facing many options, we narrow down our focus to very few of them. Although behaviors like this can be a sign of heuristics, they can actually be optimal under limited cognitive resources. Here, we study the problem of how to optimally allocate limited sampling time to multiple options, modeled as accumulators of noisy evidence, to determine the most profitable one. We show that the effective sampling capacity of an agent increases with both available time and the discriminability of the options, and optimal policies undergo a sharp transition as a function of it. For small capacity, it is best to allocate time evenly to exactly five options and to ignore all the others, regardless of the prior distribution of rewards. For large capacities, the optimal number of sampled accumulators grows sublinearly, closely following a power law as a function of capacity for a wide variety of priors. We find that allocating equal times to the sampled accumulators is better than using uneven time allocations. Our work highlights that multialternative decisions are endowed with breadth–depth tradeoffs, demonstrates how their optimal solutions depend on the amount of limited resources and the variability of the environment, and shows that narrowing down to a handful of options is always optimal for small capacities.
Visits of concern in child neurology telemedicine
Authors: Prelack Marisa , Fridinger Sara , Gonzalez Alexander K. , Kaufman Michael C. , Xian Julie , Galer Peter D. , Craig Sansanee , Abend Nicholas S. , Helbig Ingo ,   CHOP Neuroscience Center – VOC Research Group*
Published: May 2022

Aim

To characterize child neurology telemedicine visits flagged as requiring in‐person evaluation during the COVID‐19 pandemic.

Method

We analyzed 7130 audio‐video telemedicine visits between March and November 2020. Visits of concern (VOCs) were defined as telemedicine visits where the clinical scenario necessitated in‐person follow‐up evaluation sooner than if the visit had been conducted in‐person.

Results

VOCs occurred in 5% (333/7130) of visits for 292 individuals (148 females, 144 males). Providers noted technical challenges more often in VOCs (40%; 133/333) than visits without concern (non‐VOCs) (28%; 1922/6797) (p < 0.05). The median age was younger in VOCs (9 years 3 months, interquartile range [IQR] 2 years 0 months–14 years 3 months) than non‐VOCs (11 years 3 months, IQR 5 years 10 months–15 years 10 months) (p < 0.05). Median household income was lower for patients with VOCs ($74 K, IQR $55 K–$97 K) compared to non‐VOCs ($80 K, IQR $61 K–$100 K) (p < 0.05). Compared with all other race categories, families who self‐identified as Black were more likely to have a VOC (odds ratio 1.53, 95% confidence interval 1.21–2.06). Epilepsy and headache represented the highest percentages of VOCs, while neuromuscular disorders and developmental delay had a higher proportion of VOCs than other neurological disorders.

Interpretation

These findings suggest that telemedicine is an effective platform for most child neurology visits. Younger children and those with neuromuscular disorders or developmental delays are more likely to require in‐person evaluation.

What this paper adds

It is possible to successfully flag patients who need in‐person assessment.

Providers can manage issues arising during telemedicine in 95% of visits.

Visits flagged as concerning were likely unrelated to modality of patient care.

Provider concern was independent of technical difficulties for most telehealth visits.

Younger age may be correlated with need for in‐person assessment.
The effect of the conceptual metaphor theory on the teaching of orientation idioms in teaching Turkish as a foreign language
Authors: Karatay Halit , Kartallıoğlu Nurettin , Zorpuzan Sena Sapmaz , Tezel Kadir Vefa
Published: May 2022

The Challenge

Learners who attend a foreign language course aim to learn the lexis and grammar of that language and develop their basic language skills. Does this mean that idioms which are among the essential elements of any language are taught at a satisfactory level to learners? Can learners be taught a strategy that would enable them to guess the meanings of unknown idioms in the contexts they are used? This article presents the results of a study that developed activities to teach idioms that contained orientation metaphors and incorporated them into a language program.
“When nobody listens, go online”: The “807” labor movement against workplace sexism in China's tech industry
Authors: Liu Hong Yu
Published: May 2022

An online petition, signed by more than six thousand Chinese tech workers in August 2021, is the latest example of an online labor movement in the authoritarian context of China. Combining interviews and publicly available information, this article provides a descriptive account of an activist movement, explains workers' demands, and discusses the characteristics of online labor activism. It explores how Chinese tech workers fight collectively against a gender‐discriminatory workplace culture as they strive to bring justice to a sexual crime victim without affiliating themselves with official political organizations. The research findings suggest that while rising feminist consciousness has the potential to motivate collective action by workers, such motivation is highly dependent upon individual experiences at work and tends to be event‐based and of limited continuity. It argues that rising awareness of women's rights provides a new kind of legitimacy to labor activism, and a new way to express labor concerns in a context of increased criminalization of labor organizational activities in China today.
Acquired bleeding disorders
Authors: Tiede Andreas , Zieger Barbara , Lisman Ton
Published: May 2022

Acquired bleeding disorders can accompany hematological, neoplastic, autoimmune, cardiovascular or liver diseases, but can sometimes also arise spontaneously. They can manifest as single factor deficiencies or as complex hemostatic abnormalities. This review addresses (a) acquired hemophilia A, an autoimmune disorder characterized by inhibitory autoantibodies against coagulation factor VIII; (b) acquired von Willebrand syndrome in patients with cardiovascular disorders, where shear stress abnormalities result in destruction of von Willebrand factor; and (c) liver function disorders that comprise complex changes in pro‐ and anti‐hemostatic factors, whose clinical implications are often difficult to predict. The article provides an overview on the pathophysiology, diagnostic tests and state‐of‐the‐art treatment strategies.
Attitudes towards the integration of smoking cessation into lung cancer screening in the United Kingdom: A qualitative study of individuals eligible to attend
Authors: Groves Samantha , McCutchan Grace , Quaife Samantha L. , Murray Rachael L. , Ostroff Jamie S. , Brain Kate , Crosbie Philip A. J. , Yorke Janelle , Baldwin David , Field John K. , McWilliams Lorna
Published: May 2022

Introduction

There is limited research exploring how smoking cessation treatment should be implemented into lung cancer screening in the United Kingdom. This study aimed to understand attitudes and preferences regarding the integration of smoking cessation support within lung cancer screening from the perspective of those eligible.

Methods

Thirty‐one lung cancer screening eligible individuals aged 55–80 years with current or former smoking histories were recruited using community outreach and social media. Two focus groups (three participants each) and 25 individual telephone interviews were conducted. Data were analysed using the framework approach to thematic analysis.

Results

Three themes were generated: (1) bringing lung cancer closer to home, where screening was viewed as providing an opportunity to motivate smoking cessation, depending on perceived personal risk and screening result; (2) a sensitive approach to cessation with the uptake of cessation support considered to be largely dependent on screening practitioners' communication style and expectations of stigma and (3) creating an equitable service that focuses on ease of access as a key determinant of uptake, where integrating cessation within the screening appointment may sustain increased quit motivation and prevent loss to follow‐up.

Conclusions

The integration of smoking cessation into lung cancer screening was viewed positively by those eligible to attend. Screening appointments providing personalized lung health information may increase cessation motivation. Services should proactively support participants with possible fatalistic views regarding risk and decreased cessation motivation upon receiving a good screening result. To increase engagement in cessation, services need to be person‐centred.

Patient or Public Contribution

This study has included patient and public involvement throughout, including input regarding study design, research materials, recruitment strategies and research summaries.
Higher plasma renin activity is associated with increased kidney damage risk in patients with hypertension and glucose metabolic disorders
Authors: Lin Mengyue , Heizhati Mulalibieke , Gan Lin , Hong Jing , Wu Ting , Xiamili Zuhere , Tong Ling , Lin Yue , Li Nanfang
Published: May 2022

The impact of renin on kidney remain unclear among hypertensives with glucose metabolic disorders (GMD). We aimed to evaluate the association between plasma renin activity (PRA) and kidney damage in hypertensive patients with GMD. Overall, 2033 inpatients with hypertension and GMD free of chronic kidney disease (CKD) at baseline were included. CKD was defined using estimated glomerular filtration rate (eGFR) and urine protein. PRA was treated as continuous variable, and also dichotomized as high (≥0.65) or low (< 0.65) groups. The association of PRA with incident CKD was evaluated using multivariable Cox model controlling for antihypertensive medications and baseline aldosterone, and traditional parameters. Subgroup and interaction analyses were performed to evaluate heterogeneity. During a median follow‐up of 31 months, 291 participants developed CKD. The incidence was higher in high‐renin group than that in low‐renin group (54.6 vs 36.6/1000 person‐years). Significant association was observed between PRA and incident CKD, and the association was mainly driven by an increased risk for proteinuria. Each standard deviation increment in log‐transformed PRA was associated with 16.7% increased risk of proteinuria (hazard ratio = 1.167,P = .03); compared with low‐renin group, there was 78.4% increased risk for high‐renin group (hazard ratio = 1.784,P = .001). Nonlinear associations were observed between PRA and kidney damage. Higher PRA is associated with greater risk of incident kidney damage, especially for positive proteinuria, in patients with coexistence of hypertension and diabetes, independent of aldosterone. In this patient population with high risk for kidney damage, PRA may serve as an important predictor.
Involving adolescents with intellectual disability in the adaptation of self‐reported subjective well‐being measures: participatory research and methodological considerations
Authors: Davison J. , Maguire S. , McLaughlin M. , Simms V.
Published: May 2022

Background

The measurement of subjective well‐being is challenging with samples of adolescents with intellectual disability (ID) given the cognitive and linguistic difficulties they face in comprehending standardised measures, and as such is primarily based on proxy reports. The lack of appropriate tools needs to be addressed so that adolescents with ID can self‐report on their own well‐being. The current study reports on the use of participatory research methods to adapt and modify two standardised self‐report measures of subjective well‐being suitable for completion by adolescents with ID.

Method

Two special schools were recruited for this study. At each school, staff (n = 15) and pupils aged 11–17 years (n = 35) participated. A series of co‐design workshops were conducted to adapt two standardised subjective well‐being measures: Kidscreen‐10 and short‐form Warwick–Edinburgh Mental Well‐being Scale.

Results

Specific aspects for measure adaption were identified: simplifying the item wording and phrasing; inclusion of pictorial communication symbols and visual prompts to represent the meaning of items; changing of tense of questions from past to present; asking questions rather than statements; reducing 5‐point Likert scales to 3‐point or dichotomous; presenting one item at a time during administration; and developing alternate formats of the survey to ensure inclusivity.

Conclusions

This paper illustrates the value of using participatory research methods when working alongside adolescents with ID and offers methodological, as well as practical, guidance in the context of adapting subjective self‐report measures for this target group, serving as a guide to fellow researchers and clinicians interested in modifying or developing self‐report measures for adolescents with ID.
Breastfeeding and Human Lactation Curriculum Survey of Midwifery Programs in the United States
Authors: Webber Elaine , Wodwaski Nadine , Busch Deborah
Published: May 2022

Introduction

The health attributes and advantages of breastfeeding are well documented in the literature. Current research identifies the importance of comprehensive lactation knowledge among health care professionals to improve breastfeeding outcomes. Educational curricula to incorporate lactation content is necessary for student preparedness to provide competent care. Midwives are in a unique position to support, promote, and manage breastfeeding. The purpose of this study was to survey Accreditation Commission for Midwifery Education (ACME)‐accredited midwifery education programs in the United States for their breastfeeding curricular content including opportunities for clinical experiences in managing and counseling breastfeeding parents.

Methods

A descriptive survey was deployed online to midwifery programs listed by the American College of Nurse‐Midwives, with a response completion rate of 44.7%. Data collection included program descriptors, hours of lactation content, educational topics, faculty preparation, use of simulation, and clinical breastfeeding experiences.

Results

Descriptive analyses revealed differences among the midwifery education programs surveyed regarding the amount of lactation content and clinical opportunities. Two programs offer a course specific to breastfeeding, with the remaining programs providing lactation content threaded throughout their curricula; 29.4% of programs offer 3 to 4 hours of lactation content, 35.3% report 5 to 8 hours of content, and 11.8% provide at least 10 hours of content. One program reports 18+ hours of content provided in both didactic and clinical settings. All programs report providing breastfeeding clinical opportunities for students; 18% of programs offer simulation experiences. No programs report using standardized lactation clinical competencies.

Discussion

Midwives play a pivotal role in breastfeeding promotion, counseling, and clinical support. Standardization of didactic lactation education will assist programs in future curriculum mapping. Given the variability of clinical settings and patient access, creating clinical competencies and providing lactation simulation experiences may offer midwifery students a broader opportunity to gain critical skills in lactation management to best support breastfeeding families.