bluuebunny/crossref_metadata_2025 huggingface dataset:
Engineered chimeras unveil swappable modular features of fatty acid and polyketide synthase acyl carrier proteins
Authors: Cho Yae In , Armstrong Claire L. , Sulpizio Ariana , Acheampong Kofi K. , Banks Kameron N. , Bardhan Oishi , Churchill Sydney J. , Connolly-Sporing Annie E. , Crawford Callie E.W. , Cruz Parrilla Peter L. , Curtis Sarah M. , De La Ossa Lauren M. , Epstein Samuel C. , Farrehi Clara J. , Hamrick Grayson S. , Hillegas William J. , Kang Austin , Laxton Olivia C. , Ling Joie , Matsumura Sara M. , Merino Victoria M. , Mukhtar Shahla H. , Shah Neel J. , Londergan Casey H. , Daly Clyde A. , Kokona Bashkim , Charkoudian Louise K.
Published: December 2021

The strategic redesign of microbial biosynthetic pathways is a compelling route to access molecules of diverse structure and function in a potentially environmentally sustainable fashion. The promise of this approach hinges on an improved understanding of acyl carrier proteins (ACPs), which serve as central hubs in biosynthetic pathways. These small, flexible proteins mediate the transport of molecular building blocks and intermediates to enzymatic partners that extend and tailor the growing natural products. Past combinatorial biosynthesis efforts have failed due to incompatible ACP-enzyme pairings. Herein we report the design of chimeric ACPs with features of the actinorhodin polyketide synthase ACP (ACT) and of the E. coli fatty acid synthase (FAS) ACP (AcpP). We evaluate the ability of the chimeric ACPs to interact with the E. coli FAS ketosynthase FabF, which represents an interaction essential to building the carbon backbone of the synthase molecular output. Given that AcpP interacts with FabF but ACT does not, we sought to exchange modular features of ACT with AcpP to confer functionality with FabF. The interactions of chimeric ACPs with FabF were interrogated using sedimentation velocity experiments, surface plasmon resonance analyses, mechanism-based crosslinking assays, and molecular dynamics simulations. Results suggest that the residues guiding AcpP-FabF compatibility and ACT-FabF incompatibility may reside in the loop I, α-helix II region. These findings can inform the development of strategic secondary element swaps that expand the enzyme compatibility of ACPs across systems and therefore represent a critical step towards the strategic engineering of ‘unnatural’ natural products.
Learning the histone codes of gene regulation with large genomic windows and three-dimensional chromatin interactions using transformer
Authors: Lee Dohoon , Yang Jeewon , Kim Sun
Published: December 2021

The quantitative characterization of the transcriptional control by histone modifications (HMs) has been challenged by many computational studies, but still most of them exploit only partial aspects of intricate mechanisms involved in gene regulation, leaving a room for improvement. We present Chromoformer, a new transformer-based deep learning architecture that achieves the state-of-the-art performance in the quantitative deciphering of the histone codes of gene regulation. The core essence of Chromoformer architecture lies in the three variants of attention operation, each specialized to model individual hierarchy of three-dimensional (3D) transcriptional regulation including (1) histone codes at core promoters, (2) pairwise interaction between a core promoter and a distal cis-regulatory element mediated by 3D chromatin interactions, and (3) the collective effect of the pairwise cis-regulations. In-depth interpretation of the trained model behavior based on attention scores suggests that Chromoformer adaptively exploits the distant dependencies between HMs associated with transcription initiation and elongation. We also demonstrate that the quantitative kinetics of transcription factories and polycomb group bodies, in which the coordinated gene regulation occurs through spatial sequestration of genes with regulatory elements, can be captured by Chromoformer. Together, our study shows the great power of attention-based deep learning as a versatile modeling approach for the complex epigenetic landscape of gene regulation and highlights its potential as an effective toolkit that facilitates scientific discoveries in computational epigenetics.
Properties and proximity proteomics of synaptopodin provide insight into the molecular organization of the spine apparatus of dendritic spines
Authors: Falahati Hanieh , Wu Yumei , Feuerer Vanessa , De Camilli Pietro
Published: December 2021

The spine apparatus is a specialization of the neuronal ER in dendritic spines consisting of stacks of interconnected cisterns separated by a dense matrix. Synaptopodin, a specific actin binding protein of the spine apparatus, is essential for its formation, but the underlying mechanisms remain unknown. We show that synaptopodin, when expressed in fibroblasts, forms actin-rich structures with connections to the ER, and that an ER-tethered synaptopodin assembles into liquid condensates. We also identified protein neighbors of synaptopodin in spines by in vivo proximity biotinylation. We validated a small subset of such proteins and showed that they co-assemble with synaptopodin in living cells. One of them is Pdlim7, an actin binding protein not previously identified in spines, and we show its precise colocalization with synaptopodin. We suggest that the matrix of the spine apparatus has the property of a liquid protein condensate generated by a multiplicity of low affinity interactions.

Graphical abstract
Unravelling the nexus between creative self-efficacy, humble leadership, innovative work behaviour and job performance amongst physicians in public hospitals
Authors: Al Wali Joather , Muthuveloo Rajendran , Teoh Ai Ping
Published: December 2021

Purpose

The study aims to examine the relationship between innovative work behaviour (IWB) and JP amongst physicians in Iraq public hospitals. The study also determines the effects of creative self-efficacy (CSE) and humble leadership (HL) on IWB. Besides, the study investigates the mediating role of IWB on the relationship between CSE and JP as well as between HL and JP.

Design/methodology/approach

A total of 332 respondents participated in the survey, although 173 responses were utilised after data screening. The study employs the structural equation modelling via partial least squares (PLS-SEM) to ascertain the relationship between the variables.

Findings

Evidence from the study indicates that IWB has a positive relationship with JP, whilst CSE and HL are significant determinants of IWB amongst physicians in Iraq public hospitals. The study provides evidence that IWB plays a positive mediating role in the relationship between CSE and JP as well as between HL and JP amongst physicians in Iraq public hospitals.

Originality/value

The study implies that the JP of physicians in Iraq public hospitals can be enhanced by IWB, whilst the latter can be improved by CSE and HL. The influences of CSE and HL on JP can be boosted by IWB. Hence, efforts to promote IWB should be vigorously pursued by Iraq public hospitals to foster the physicians' JP.
A cognitive model for understanding fraudulent behavior in construction industry
Authors: Hu Huimin , Deng Xiaopeng , Mahmoudi Amin
Published: December 2021

Purpose

Previous fraud studies focused on the influence of external environmental factors rather than the actor's own cognition or psychological factors. This paper aims to explore the influence of cognitive factors on people's intention to commit fraud in the construction industry.

Design/methodology/approach

A scenario-based questionnaire survey was conducted with 248 Chinese construction practitioners. Partial least squares structural equation modeling (PLS-SEM) was used to analyze the data.

Findings

The findings showed that perceived threat possibility and perceived threat severity positively affected people's attitudes towards fraud. The reward for compliance and response cost had adverse effects on people's attitudes. Attitude towards fraud and response efficacy directly influenced people's intentions to commit fraud.

Research limitations/implications

The limitations of this study are that only behavioral intention data were collected, and a single scenario was designed. Despite these limitations, this study proposed a cognitive model to understand fraud in the construction industry and provided an empirical analysis using data from Chinese construction practitioners.

Originality/value

This study reveals the impact of cognitive factors on fraud in the construction industry. The results expand the understanding of fraud and propose a cognitive intervention framework to reduce fraud.
Effects of innovative finance, strategy, organization and performance: a case study of company
Authors: Sonmez Cakir Fatma , Adiguzel Zafer
Published: December 2021

Purpose

The aim of the research is to analyze sustainability in energy companies in terms of financial innovation, innovation strategy and organizational innovation.

Design/methodology/approach

The analysis of this research was done by using the Mplus 7 package program, and the research model was tested using the existing latent variables and their expressions. Data from 298 administrative staff (white collar) working in companies operating in the energy sector were analyzed.

Findings

Both independent and mediation effects of financial innovation and innovation strategy positively affect sustainability performance. Therefore, it can be concluded that in order for sustainability performance to be positive, importance should be given to financial innovation, innovation strategy and organizational innovation activities.

Research limitations/implications

As the data were collected from energy companies in this research, it is not correct to generalize the evaluations. Therefore, in terms of the limitations of the research, the sector and sample size should be taken into account in future studies.

Originality/value

This research conducted in energy companies focuses on the importance of sustainability and has a unique value in the literature as the data is collected and analyzed from white-collar employees.
Revisiting the food security system in India in the pandemic era: the case of a Southern Indian state
Authors: Dar Vandita , Sethi Madhvi , Baby Saina , Dinesh Kumar S. , Shrinivas R.
Published: December 2021

Purpose

The objective of this paper was twofold-revisiting the in-kind public distribution system (PDS) – India's flagship food security intervention and seeking beneficiary perspectives on its efficacy. The feasibility of cash transfers as an alternative mechanism is also examined, especially in the context of the COVID-19 pandemic.

Design/methodology/approach

Primary and secondary data from the southern Indian state of Tamil Nadu were used. In-depth interviews with beneficiaries using phenomenology were conducted to evaluate their perception and willingness to shift to a cash-based PDS in the pre and post-pandemic periods. Secondary district-level data were also used to ascertain institutional preparedness for this shift.

Findings

In-depth interviews of 105 beneficiaries revealed valuable insights, which seem to have significantly changed post-pandemic. Beneficiaries in the post-pandemic period seem much more inclined toward cash transfers, though a combination of cash plus in-kind benefits seems to be strongly preferred. Secondary results pointed out to the lack of institutional preparedness in financial inclusion. The research suggested that while the existing PDS needs to be overhauled, policymakers should look at a model of cash plus in-kind transfers as a probable alternative to pure cash transfers.

Originality/value

There is a dearth of in-depth state-specific studies on beneficiary perception of PDS, and this is important since the economic and sociocultural milieu in each region is unique. Being the only state with universal food security, its experience could yield important insights for other states or even middle or low-income countries similar to India.
Exploring indigenous conflict resolution mechanisms between the Awi and Gumuz ethnic communities in Zigem Woreda, Ethiopia
Authors: Mengstie Missaye Mulatie
Published: December 2021

Purpose

The purpose of this study is to explore indigenous conflict resolution mechanisms for resolving ethnic-based conflicts between the Awi and Gumuz communities in Ethiopia.

Design/methodology/approach

This study followed a qualitative research approach and it has a case study design that is appropriate to collect in-depth information about indigenous mechanisms of resolving conflicts that arise between Awi and Gumuz ethnic groups. Data were collected through in-depth interviews and document review.

Findings

The results revealed that the Awi and Gumuz ethnic groups resolve conflict through the elder council or shimigilina. This indigenous mechanism conflict resolution mechanism is well recognized, accepted and respected both by the Awi and Gumuz ethnic groups. Shimiglina has different phases and rituals which are finally concluded by kale-mehala (oath) or promising not to take revenge and harm. The Awi and Gumuz ethnic groups view shimigilina as a vital and effective conflict resolution mechanism.

Practical implications

This study clearly indicated important implications for policy, practice and future research. The Awi and Gumuz communities have used the elders’ council (shimiglina) to solve ethnic-based conflicts for a long time. Therefore, there should be policy frameworks at different levels (national, regional and local) for the integration of the elders’ council with the formal justice system. Put in other words, this indigenous conflict resolution mechanism should be properly organized and institutionalized. However, a comprehensive study should be conducted to understand how to organize and institutionalize this indigenous conflict resolution mechanism.

Originality/value

This is an original study that contributes to peacebuilding by discovering the role of indigenous knowledge in conflict resolution and peacebuilding.
The impact of qualified audit opinion on stock returns: an empirical study at Amman stock exchange
Authors: Bayo Flees Rana , Mouselli Sulaiman
Published: December 2021

Purpose

This paper aims to investigate the impact of qualified audit opinions on the returns of stocks listed at Amman Stock Exchange (ASE) after the introduction of the recent amendments by the International Auditing and Assurance Standard Board (IAASB) on audits reporting and conclusions. It further investigates if results differ between first time qualified and sequenced qualifications, and between plain qualified opinion and qualifications with going concern.

Design/methodology/approach

Audit opinions’ announcements and stock returns data are collected from companies’ annual reports for the fiscal years 2016 to 2019 while stock returns are computed from stock closing prices published at ASE website. The authors apply the event study approach and use the market model to calculate normal returns. Cumulative abnormal returns (CARs) and average abnormal returns (AARs) are computed for all qualified audit opinions’ announcements.

Findings

The empirical evidence suggests that investors at ASE do not react to qualified audit opinions announcements. That is, the authors find an insignificant impact of qualified audit opinion announcements on stock returns using both CAR and AAR estimates. The results are robust to first time and sequenced qualifications, and for qualifications with going concern. Results are also robust to the use of risk adjusted market model.

Research limitations/implications

The insignificant impact of qualified audit opinions on stock returns have two potential conflicting research implications. First, the new amendments introduced to auditors’ report made them more informative and reduce the negative signals contained in the qualified opinions. That is, investors are now aware of the real causes of qualifications and not overreacting to the qualified opinion. Second, the documented insignificant impact confirms that ASE is not a semi-strong form efficient.

Practical implications

The apparent excessive use of qualifications should ring the bell on whether auditors misuse their power or companies are really in trouble. Hence, the Jordanian regulatory bodies need to warn auditors against the excessive use of qualifications on the one hand, and to raise the awareness of investors on the implications of auditors’ opinions on the other hand.

Originality/value

This study is innovative in twofold. First, it explores the impact of qualified audit opinions on stock returns after the introduction of new amendments by IAASB at ASE. In addition, it uses event study approach and distinguishes between first time qualified and sequenced qualifications, and between plain qualified opinion and qualifications with going concern. The results are consistent with efficient market theory and behavioral finance explanations.
Leadership competencies of first-line nurse managers: a quantitative study
Authors: Paarima Yennuten , Kwashie Atswei Adzo , Asamani James Avoka , Ofei Adelaide Maria Ansah
Published: December 2021

Purpose

This paper aims to examine the leadership competencies of first-line nurse managers (FLNMs) at the unit level in the eastern region of Ghana.

Design/methodology/approach

The paper is a quantitative cross-section design.

Findings

Nurse managers exhibited a moderate level of knowledge and ability to apply leadership competencies. Gender, rank, qualification, professional experience, management experience and management training jointly predicted the leadership competencies of FLNMs [(R2 = 0.158, p = 0.016]. However, only management training was a significant predictor in the model.

Practical implications

Inappropriate leadership competencies have severe consequences for patients and staff outcomes. This situation necessitates a call for a well-structured program for the appointment of FLNMs based on competencies.

Originality/value

This study is the first in Ghana which we are aware of that examined the leadership competencies at the unit level that identifies predictors of leadership competencies.
Great minds think alike: does leader-follower similarity in construal level of the work enhance leader-member exchange quality?
Authors: Emirza Sevgi , Katrinli Alev
Published: December 2021

Purpose

The purpose of this study is to investigate whether leader-follower similarity in construal level of the work, which indicates the degree of abstraction applied to mental representation of the work, influences the quality of interpersonal relationship at work.

Design/methodology/approach

First, an interview study was conducted to adapt the work-based construal-level (WBCL) scale. Then, a survey study was conducted for hypothesis testing. Data collected from 245 matched supervisor-subordinate dyads were analyzed using multi-level modeling.

Findings

Results revealed that dyadic similarity in work-domain construal level is positively related to leader-member exchange (LMX) quality. As a leader and a follower become similar to each other in terms of mental representation (i.e. construal level) of work, they experience higher relationship quality.

Originality/value

This study enhances the current knowledge of the role of cognition and cognitive similarity in leadership processes.
Exploring the social activity of open research data on ResearchGate: implications for the data literacy of researchers
Authors: Raffaghelli Juliana Elisa , Manca Stefania
Published: December 2021

Purpose

Although current research has investigated how open research data (ORD) are published, researchers' behaviour of ORD sharing on academic social networks (ASNs) remains insufficiently explored. The purpose of this study is to investigate the connections between ORDs publication and social activity to uncover data literacy gaps.

Design/methodology/approach

This work investigates whether the ORDs publication leads to social activity around the ORDs and their linked published articles to uncover data literacy needs. The social activity was characterised as reads and citations, over the basis of a non-invasive approach supporting this preliminary study. The eventual associations between the social activity and the researchers' profile (scientific domain, gender, region, professional position, reputation) and the quality of the ORD published were investigated to complete this picture. A random sample of ORD items extracted from ResearchGate (752 ORDs) was analysed using quantitative techniques, including descriptive statistics, logistic regression and K-means cluster analysis.

Findings

The results highlight three main phenomena: (1) Globally, there is still an underdeveloped social activity around self-archived ORDs in ResearchGate, in terms of reads and citations, regardless of the published ORDs quality; (2) disentangling the moderating effects over social activity around ORD spots traditional dynamics within the “innovative” practice of engaging with data practices; (3) a somewhat similar situation of ResearchGate as ASN to other data platforms and repositories, in terms of social activity around ORD, was detected.

Research limitations/implications

Although the data were collected within a narrow period, the random data collection ensures a representative picture of researchers' practices.

Practical implications

As per the implications, the study sheds light on data literacy requirements to promote social activity around ORD in the context of open science as a desirable frontier of practice.

Originality/value

Researchers data literacy across digital systems is still little understood. Although there are many policies and technological infrastructure providing support, the researchers do not make an in-depth use of them.

Peer review

The peer-review history for this article is available at: https://publons.com/publon/10.1108/OIR-05-2021-0255.
Supporting girls and young women victims of sexual harassment in schools: “me and you and everyone we know”
Authors: Goodman Anthony , Calestani Melania
Published: December 2021

Purpose

This study aims to highlight an innovative project, across three European countries, namely, Italy, Sweden and Romania, that used pictorial designs to empower young women to demand the right to live without sexual harassment.

Design/methodology/approach

Abstract figures in terms of race and gender of young people were produced on cards, which allowed the imagination of the viewer to interpret and discuss these images freely. Other cards had definitions and scenarios. The cards generated discussion and comments both with the young participants and educational professionals.

Findings

Using the cards produced a rich set of responses from the students. Not all recognised that what was happening between young men and women was sexual harassment. There was a need to develop the concept of empathy and personal responsibility for behaviour and etiquette between the sexes. The response from professionals also varied in terms of sympathy and understanding.

Research limitations/implications

The three countries had different degrees of openness to addressing sexual harassment of girls in schools. The results may not be generalisable to the UK and researchers would like to use the tool developed in other countries.

Practical implications

The focus groups with young people in schools highlighted different attitudes towards sexual harassment in girls and young women, between the young women and young men, and the variations in the three countries. There was a need to educate professionals of the long-term impact of sexual violence and harassment.

Social implications

The research revealed the importance of producing a tool (the cards), which enabled young people to discuss sexual harassment in a focused way. Young women will gain in confidence to challenge sexual and oppressive behaviour.

Originality/value

This paper gives a voice to young people to discuss an issue, sexual harassment, that is addressed to varying degrees in the countries involved. The competition for young people to produce posters led to some amazing creative ideas.
Winter always comes: social enterprise in times of crisis
Authors: Weaver Rasheda , Blakey Chyanne Lanae
Published: December 2021

Purpose

This study aims to outline the importance of distinguishing between different types of societal crises and the role that plays in how social enterprises may respond to crises at hand.

Design/methodology/approach

Previous literature is used to distinguish between various types of societal crises discussed in the study. Social enterprise responses to the COVID-19 pandemic, economic recession and the racial uprising in the USA that all erupted at the start of the 2020 decade are explored to illustrate the need for different responses to each.

Findings

The origin and manifestation of crises differ in that they may have public health, natural, economic or even intentionally man-made origins. In addition, in times of crisis, social enterprises must be prepared to innovate, adapt or at least manage the effects of one or more crises on their organizations. These innovations may be social, technology or economic innovations.

Research limitations/implications

This study contributes to knowledge about the role and value of social enterprise as a tool for addressing societal issues. The three types of crises explored in this paper will likely reoccur and evolve to manifest in new ways. As such, it is imperative that research on the efficacy of social enterprises during times of crisis are conducted to inform practice, policy and future research.

Practical implications

This study aims to inform and encourage institutions, particularly social enterprises, to recognize that “winter always comes.” Crises always happen in life and how organizations respond to such crises will differ based on the type of crisis at hand. This study particularly contributes to knowledge by emphasizing the need for social enterprises to think about both economic uncertainty and the role they play in addressing crises in the long-term, not just when they occur.

Originality/value

To the best of the authors’ knowledge, this study is one of the first to explore the role and value of social enterprises as a tool for combatting major social crises such as racism, pandemics and recessions.
English version of guidelines for the management of asteatosis 2021 in Japan
Authors: Saeki Hidehisa , Tsunemi Yuichiro , Arai Satoru , Ichiyama Susumu , Katoh Norito , Kikuchi Katsuko , Kubo Akiharu , Terui Tadashi , Nakahara Takeshi , Futamura Masaki , Murota Hiroyuki , Igarashi Atsuyuki
Published: December 2021

This is the English version of guidelines for the management of asteatosis 2021 in Japan. Asteatosis is a synonym of xerosis found in a wide range of diseases that induce dry skin through impaired functions of either water retention of the stratum corneum or skin covering with acid mantle. Patients with asteatosis may be accompanied by pruritus. Moisturizers are the first‐line treatment for asteatosis and their adequate use must be recommended. The main purpose of the present guidelines is to define skin symptoms requiring treatment with moisturizers for medical use in patients with asteatosis. If the deterioration of marked scaling or scratch marks is predicted, therapeutic intervention with moisturizers for medical use should be considered even in the absence of pruritus. Regarding six important points requiring decision‐making in clinical practice (clinical questions), we evaluated the balance between the benefits and harm of medical interventions in reference to previous reports of clinical research, and presented the recommendation grades and evidence levels to optimize the patient outcome by medical interventions.
An examination of anti‐violence human resource management practices in the context of health care and aged care
Authors: Shao Bo , Dina Pariona‐Cabrera Patricia , Guo Yongxing , Chrisfield Kathy , Bartram Timothy
Published: December 2021

Although accumulated research has demonstrated the negative impacts of workplace violence and called for effective solutions from a human resource management (HRM) perspective, a valid measure of anti‐violence HRM practices is missing. In this paper, we develop a scale of anti‐violence HRM practices that is critical for both theoretical advancement and managerial practices in health care and aged care contexts. Through an inductive approach in Study 1, we generated items for the scale to be used in health care and aged care contexts, which we then subjected to a content validity test in Study 2. Using the newly developed scale, we further demonstrated in Study 3 that anti‐violence HRM practices that are implemented in aged care facilities reduce workers' experienced violence, improve workers' emotional wellbeing, and enhance workers' organisational and career commitment.
Differential effects of environmental climatic variables on parasite abundances in blue tit nests during a decade
Authors: CASTAÑO‐VÁZQUEZ Francisco , MERINO Santiago
Published: December 2021

Models on climate change have predicted an increase of temperature over the earth's surface with potential drastic effects on living organisms. We analyzed the relationships between climatic conditions (temperature, rainfall, and wind speed) and the abundance of blood‐sucking flying insects (biting midges and blackflies) and nest‐dwelling ectoparasites (mites, fleas, and blowflies) collected from blue tit nests during bird breeding seasons for a period of 10 years. Average temperature, rainfall, and wind speed showed significant differences among years. Temperature and wind speed increased during the period of study while rainfall decreased. Biting midge, blackfly, and blowfly abundances increased across years but not flea and mite abundances. Hatching date decreased and brood size increased across years. Independently of year variation, parasites were related to climatic variables. For example, biting midge, blowfly, mite, and flea abundances were positive and significantly related to average temperature. We also found a positive and significant relationship between abundances of Haemoproteus infections and biting midge abundances during the first year of life of birds out of nests. However, abundance and prevalence of Lankesterella infections in yearlings were positive and significantly related to mite abundances during the year of birth of birds. Leucocytozoon and Lankesterella infections were also significantly related to climatic variables and Haemoproteus and Lankesterella infections increased across years. In addition, body condition of adult females and males were negatively related to flea larvae and blowfly abundance respectively. Nestling body condition was also negatively related to biting midge abundance. Changes in climatic conditions across years could therefore affect several parasites of birds but also to birds themselves.
Clinical characteristics and prognostic model for extensive‐stage small cell lung cancer: A retrospective study over an 8‐year period
Authors: Ni Jun , Zhang Xiaotong , Wang Hanping , Si Xiaoyan , Xu Yan , Zhao Jing , Chen Minjiang , Zhang Li , Wang Mengzhao
Published: December 2021

Background

Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor with a short replication time and a rapid growth rate. Prognostic factors for SCLC in clinical practice are scarce. Retrospective analysis of 8‐year extensive‐stage SCLC data from the Department Respiratory and Intensive Care Unit, Peking Union Medical College Hospital (Beijing, China) was performed to develop a risk prediction model that can facilitate the identification of extensive‐stage SCLC with differing prognosis in clinical practice.

Methods

A retrospective analysis of data from patients with extensive‐stage SCLC at a single‐center from January 2013 to January 2021, including age, sex, ECOG physical score, immunohistochemistry (CgA, Syn, CD56, TTF1, and Ki67), staging, treatment regimen, laboratory examinations, and survival period, was performed. Clinical variables with potential prognostic significance were screened by univariate Cox analysis. Next, multifactor Cox risk prediction regression analysis was performed to establish an extensive‐stage SCLC risk prognostic model. Survival curves and ROC curves for high and low risk groups were plotted according to risk scores. Nomogram and calibration curves were developed to assess the accuracy of the risk prediction model.

Results

This study included 300 patients who were diagnosed with extensive‐stage SCLC at our center from January 2013 to January 2021. The most common first presentation was respiratory symptoms, especially cough (162, 54%). The most common extra‐thoracic metastatic organs were bone (36.3%), liver (24.7%), brain (15.7%), and adrenal glands (15.7%). A total of 99% of patients received first‐line systemic therapy, with 86.3% of patients treated with platinum‐etoposide and 10.7% of patients treated with immune checkpoint inhibitor combined with platinum‐etoposide backbone. First‐line progression‐free survival was up to 198 days, and the median OS was 439 days. After Cox regression screening and backward stepwise selection, “time from initial therapy to relapse or progression (PFS1), liver metastases, adrenal metastases, M stage and first‐line treatment pattern” were retained to establish a prognostic model with an AUC value of 0.763. The prognostic model was shown as a nomogram with good agreement between predicted and observed outcomes.

Conclusions

The first‐line treatment of SCLC patients admitted to our hospital in the past 8 years was relatively standardized, and the progression‐free survival and OS were slightly longer than those reported in the literature. We developed a prognostic risk score model for extensive‐stage SCLC to calculate individual survival in clinical practice.
Emerging rejuvenation strategies—Reducing the biological age
Authors: Zhang Bohan , Trapp Alexandre , Kerepesi Csaba , Gladyshev Vadim N.
Published: December 2021

Several interventions have recently emerged that were proposed to reverse rather than just attenuate aging, but the criteria for what it takes to achieve rejuvenation remain controversial. Distinguishing potential rejuvenation therapies from other longevity interventions, such as those that slow down aging, is challenging, and these anti‐aging strategies are often referred to interchangeably. We suggest that the prerequisite for a rejuvenation intervention is a robust, sustained, and systemic reduction in biological age, which can be assessed by biomarkers of aging, such as epigenetic clocks. We discuss known and putative rejuvenation interventions and comparatively analyze them to explore underlying mechanisms.
Host plants and associated trophobionts of the weaver ant Oecophylla longinoda Latreille (Hymenoptera Formicidae) in Benin
Authors: Vayssières Jean‐François , Grechi Isabelle , Sinzogan Antonio , Ouagoussounon Issa , Todjihoundé Raymond , Modjibou Soumanou , Tossou Jean‐Claude , Adandonon Appolinaire , Kikissagbé Cinthia , Tamò Manuele , Goergen Georg , Chailleux Anaïs , Germain Jean‐François , Adomou Aristide
Published: December 2021

The African weaver ant Oecophylla longinoda builds woven leaf nests inside tree canopies and is a major conservation biocontrol agent in sub‐Saharan Africa. Weaver ant colonies provide well‐protected and resource‐rich environments for many associated trophobionts, thereby boosting their establishment on host plants.

There is very little published literature on O. longinoda, their hosts plants and their associated trophobionts in West Africa. These tri‐trophic interactions were studied over a period of four consecutive years (2010–2013) from south to north Benin.

Our fieldwork revealed that all O. longinoda colonies were consistently associated with trophobionts. Oecophylla longinoda nests were recorded on 82 plant species belonging to 30 families, with 35 associated trophobiont species representing 11 families.

Among cultivated plants, Mangifera indica was the most common species hosting O. longinoda, while Sarcocephalus latifolius the most frequent native one. Among trophobionts, Parasaissetia nigra, Udinia catori, Udinia farquharsoni (Coccidae) and Stictococcus sjostedti (Stictococcidae) were the most common hemipterans associated with O. longinoda.

We identified a wide range of host plants that could be preserved (or planted) to promote the establishment of weaver ants to control different insect pests in fruit plantations in sub‐Saharan Africa. When planted around fruit plantations with their nests and tended hemipterans, these host plants could facilitate biocontrol of mango fruit flies (Tephritidae) and cashew bugs (Coreidae, Miridae), by O. longinoda in the fruit plantations.
Editorial: risk of loss of response to anti TNFα in patients with inflammatory bowel diseases – the longer the less? Authors' reply
Authors: Schultheiss Johannes P. D. , Mahmoud Remi , Fidder Herma H. , Oldenburg Bas
Published: December 2021

LINKED CONTENT

This article is linked to Schultheiss et al papers. To view these articles, visit https://doi.org/10.1111/apt.16605 and https://doi.org/10.1111/apt.16648
Small rocky outcrops: Natural features to promote biodiversity in oak wood‐pastures
Authors: Chozas Sergio , Tapia Susana , Palmeirim Jorge , Alegria Carla , Correia Otília
Published: December 2021

Aims

The Iberian oak wood‐pastures are unique agroforestry systems supporting high levels of biodiversity and ecosystem services. Small rocky outcrops are geological features commonly found in these systems and constitute biodiversity reservoirs, protecting sensitive species from grazing and farming activities. We aimed to assess the relevance of including rocky outcrop conservation within wood‐pastures to increase biodiversity. To achieve this goal, we studied the plant communities occurring within the outcrops and in the wood‐pasture matrix to evaluate the impact of rocky outcrops on the overall plant taxonomic and functional diversities of these systems.

Location

Montemor‐o‐Novo (Alentejo, Portugal).

Methods

We sampled 102 plant communities occurring in outcrops and the adjacent wood‐pasture matrix, and analysed alpha, beta, gamma and functional diversities. We identified the main intrinsic factors affecting outcrop plant composition and their functional groups using Linear and Generalized Linear Mixed models, and characterized the effect of outcrop size through Generalized Additive Models.

Results

We found plant richness to be similar in wood‐pasture matrix and outcrops. However, β‐diversity analysis revealed a high species turnover between both communities. Functional indices indicated higher plant functional diversity in outcrops and trait analyses identified three functional groups dissimilarly distributed in both communities: (a) perturbation‐ and stress‐sensitive plants, with outcrops constituting an important refuge for this group; and (b) grazing‐tolerant and (c) weedy herbs dominating the wood‐pastures. Finally, we also found increased plant richness in outcrops with a longer length for their minor axis, i.e. wider outcrops, and greater rock cover area.

Conclusions

Our results indicate that the presence of small rocky outcrops in evergreen oak wood‐pastures greatly increases their gamma and functional diversities. Consequently, outcrop protection strongly impacts overall wood‐pasture biodiversity and underlines the suitability of including outcrop conservation as a cost‐effective solution capable of increasing biodiversity in these agroforestry systems.
Proton pump inhibitor use and hearing loss in patients with type 2 diabetes: Evidence from a hospital‐based case‐control study and a population‐based cohort study
Authors: Yee Jeong , Han Hye Won , Gwak Hye Sun
Published: December 2021

Objectives

This study aimed to investigate the association between proton pump inhibitor (PPI) use and risk of sensorineural hearing loss (SNHL) or tinnitus in patients with type 2 diabetes using hospital‐ and population‐based data.

Methods

For the case‐control study using the Asan Biomedical Research Environment database, the characteristics between cases and sex‐, age‐ and index‐year‐matched controls were compared by the chi‐squared test. Conditional logistic regression was used to estimate the odds ratios (ORs). For the cohort study using the Korean National Health Insurance Service – National Sample Cohort, the hazard ratios (HRs) for SNHL or tinnitus associated with PPI use were analysed by the Cox proportional hazard regression model.

Results

The case‐control study included 1379 cases and 5512 matched controls. After adjustment, PPI use was associated with an increased risk of SNHL or tinnitus (OR 1.61, 95% confidence interval [CI] 1.30‐1.99). The ORs were higher for current or recent use of PPI and high average daily dose. In the cohort study including 17 233 pairs of PPI users and nonusers after propensity score matching, the risk of SNHL or tinnitus increased in PPI users compared with nonusers (HR 1.50, 95% CI 1.40‐1.61). In the stratified analyses, risks remained significant and the magnitude of association was relatively high in those of younger age, patients without gastroesophageal reflux disease and patients not receiving histamine 2 receptor blockers.

Conclusions

Our study suggests that PPI use is associated with an increased risk of SNHL or tinnitus. Given the widespread use of PPIs, the potential ototoxic effects of PPIs remain an important concern.
High prevalence of TERT aberrations in myxoid liposarcoma: TERT reactivation may play a crucial role in tumorigenesis
Authors: Kunieda Junko , Yamashita Kyoko , Togashi Yuki , Baba Satoko , Sakata Seiji , Inamura Kentaro , Ae Keisuke , Matsumoto Seiichi , Machinami Rikuo , Kitagawa Masanobu , Takeuchi Kengo
Published: December 2021

Myxoid liposarcoma (MLPS) is genetically characterized by FUS‐DDIT3 or EWSR1‐DDIT3 gene fusion and the high frequency of hotspot mutations (C228T or C250T) in the promoter region of telomerase reverse transcriptase (TERT) that encodes the TERT protein. The latter leads to telomerase reactivation, a mechanism of telomere maintenance. Although the TERT promoter hotspot mutation is a poor prognostic factor in various tumors, its effect on MLPS has not been reported in detail. In the present study, we examined the clinicopathological characteristics, prognosis, and telomere maintenance mechanisms in 83 primary tumor samples of MLPS, which were resected surgically at the Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan, from 2008 to 2020. TERT promoter hotspot mutations were observed in 77% (63/82) cases, and alternative lengthening of telomeres (ALT) was absent in all cases. Among the cases without TERT promoter hotspot mutations, TERT rearrangements, and minor point mutations in the TERT promoter region were found in 3 and 2 cases, respectively. TERT mRNA expression was observed consistently even in patients for whom no genomic TERT aberrations were detected, and the presence of TERT promoter hotspot mutation did not correlate significantly with either overall and metastasis‐free survival (P = .56, P = .83, respectively) or clinicopathological features. Therefore, patients with MLPS characteristically shows TERT expression and a high prevalence of TERT aberrations. Our findings suggest that TERT aberration is not prognostic factor, but might occur at an early stage and play a key role in tumorigenesis.
Cancer immunotherapy using artificial adjuvant vector cells to deliver NY‐ESO‐1 antigen to dendritic cells in situ
Authors: Fujii Shin‐ichiro , Yamasaki Satoru , Hanada Kenichi , Ueda Shogo , Kawamura Masami , Shimizu Kanako
Published: December 2021

NY‐ESO‐1 is a cancer/testis antigen expressed in various cancer types. However, the induction of NY‐ESO‐1‐specific CTLs through vaccines is somewhat difficult. Thus, we developed a new type of artificial adjuvant vector cell (aAVC‐NY‐ESO‐1) expressing a CD1d‐NKT cell ligand complex and a tumor‐associated antigen, NY‐ESO‐1. First, we determined the activation of invariant natural killer T (iNKT) and natural killer (NK) cell responses by aAVC‐NY‐ESO‐1. We then showed that the NY‐ESO‐1‐specific CTL response was successfully elicited through aAVC‐NY‐ESO‐1 therapy. After injection of aAVC‐NY‐ESO‐1, we found that dendritic cells (DCs) in situ expressed high levels of costimulatory molecules and produced interleukn‐12 (IL‐12), indicating that DCs undergo maturation in vivo. Furthermore, the NY‐ESO‐1 antigen from aAVC‐NY‐ESO‐1 was delivered to the DCs in vivo, and it was presented on MHC class I molecules. The cross‐presentation of the NY‐ESO‐1 antigen was absent in conventional DC‐deficient mice, suggesting a host DC‐mediated CTL response. Thus, this strategy helps generate sufficient CD8+ NY‐ESO‐1‐specific CTLs along with iNKT and NK cell activation, resulting in a strong antitumor effect. Furthermore, we established a human DC‐transferred NOD/Shi‐scid/IL‐2γcnull immunodeficient mouse model and showed that the NY‐ESO‐1 antigen from aAVC‐NY‐ESO‐1 was cross‐presented to antigen‐specific CTLs through human DCs. Taken together, these data suggest that aAVC‐NY‐ESO‐1 has potential for harnessing innate and adaptive immunity against NY‐ESO‐1‐expressing malignancies.
Oncogenic FGFR1 mutation and amplification in common cellular origin in a composite tumor with neuroblastoma and pheochromocytoma
Authors: Tasaka Keiji , Ueno Hiroo , Yamasaki Kai , Okuno Takahiro , Isobe Tomoya , Kimura Shunsuke , Umeda Katsutsugu , Hara Junichi , Ogawa Seishi , Takita Junko
Published: December 2021

Neuroblastoma (NB) and pheochromocytoma (PCC) are derived from neural crest cells (NCCs); however, composite tumors with NB and PCC are rare, and their underlying molecular mechanisms remain unknown. To address this issue, we performed exome and transcriptome sequencing with formalin‐fixed paraffin‐embedded (FFPE) samples from the NB, PCC, and mixed lesions in a patient with a composite tumor. Whole‐exome sequencing revealed that most mutations (80%) were shared by all samples, indicating that NB and PCC evolved from the same clone. Notably, all samples harbored both mutation and focal amplification in the FGFR1 oncogene, resulting in an extraordinarily high expression, likely to be the main driver of this tumor. Transcriptome sequencing revealed undifferentiated expression profiles for the NB lesions. Considering that a metastatic lesion was also composite, most likely, the primitive founding lesions should differentiate into both NB and PCC. This is the first reported case with composite‐NB and PCC genetically proven to harbor an oncogenic FGFR1 alteration of a common cellular origin.
Growth in emotion understanding across early childhood: A cohort‐sequential model of firstborn children across the transition to siblinghood
Authors: Tan Lin , Volling Brenda L. , Gonzalez Richard , LaBounty Jennifer , Rosenberg Lauren
Published: December 2021

Emotion understanding develops rapidly in early childhood. Firstborn children (N = 231, 55% girls/45% boys, 86% White, 5% Black, 3% Asian, 4% Latinx, Mage = 29.92 months) were recruited into a longitudinal study from 2004 to 2008 in the United States and administered a series of tasks assessing eight components of young children's emotion understanding from ages 1 to 5. Cohort sequential analysis across three cohorts (1‐, 2‐, and 3‐year‐olds) demonstrated a progression of children's emotion understanding from basic emotion identification to an understanding of false‐belief emotions, even after controlling for children's verbal ability. Emotion understanding scores were related to children's theory of mind and parent reports of empathy, but not emotional reactivity, providing evidence of both convergent and discriminant validity.