bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient quantification of lipid packing defect sensing by amphipathic peptides; comparing Martini 2 & 3 with CHARMM36
Authors: van Hilten Niek , Stroh Kai Steffen , Risselada Herre Jelger
Published: March 2022

In biological systems, proteins can be attracted to curved or stretched regions of lipid bilayers by sensing hydrophobic defects in the lipid packing on the membrane surface. Here, we present an efficient end-state free energy calculation method to quantify such sensing in molecular dynamics simulations. We illustrate that lipid packing defect sensing can be defined as the difference in mechanical work required to stretch a membrane with and without a peptide bound to the surface. We also demonstrate that a peptide’s ability to concurrently induce excess leaflet area (tension) and elastic softening – a property we call the ‘characteristic area of sensing’ (CHAOS) – and lipid packing sensing behavior are in fact two sides of the same coin. In essence, defect sensing displays a peptide’s propensity to generate tension. The here-proposed mechanical pathway is equally accurate yet, computationally, about 40 times less costly than the commonly used alchemical pathway (thermodynamic integration), allowing for more feasible free energy calculations in atomistic simulations. This enabled us to directly compare the Martini 2 and 3 coarse-grained and the CHARMM36 atomistic force-fields in terms of relative binding free energies for six representative peptides including the curvature sensor ALPS and two antiviral amphipathic helices (AH). We observed that Martini 3 qualitatively reproduces experimental trends, whilst producing substantially lower (relative) binding free energies and shallower membrane insertion depths compared to atomistic simulations. In contrast, Martini 2 tends to overestimate (relative) binding free energies. Finally, we offer a glimpse into how our end-state based free energy method can enable the inverse design of optimal lipid packing defect sensing peptides when used in conjunction with our recently developed Evolutionary Molecular Dynamics (Evo-MD) method. We argue that these optimized defect sensors – aside from their biomedical and biophysical relevance – can provide valuable targets for the development of lipid force-fields.

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Pinch2 is a novel regulator of myelination in the Central Nervous System
Authors: Paes de Faria J , Vale-Silva RS , Fässler R , Werner HB , Relvas JB
Published: March 2022

The extensive morphological changes of oligodendrocytes during axon ensheathment and myelination involve assembly of the Ilk-Parvin-Pinch (IPP) heterotrimeric complex of proteins to relay essential mechanical and biochemical signals between integrins and the actin cytoskeleton. Binding of Pinch 1 and 2 isoforms to Ilk is mutually exclusive and allows the formation of distinct IPP complexes with specific signaling properties. Using tissue-specific conditional gene ablation in mice, we reveal an essential role for Pinch2 during central nervous system myelination. UnlikePinch1-gene ablation, loss ofPinch2in oligodendrocytes results in hypermyelination and in the formation of pathological myelin outfoldings in white matter regions. These structural changes concurred with inhibition of Rho GTPases RhoA and Cdc42 activities and phenocopied aspects of myelin pathology observed in corresponding mouse mutants. We propose a dual role for Pinch2 in preventing excess of myelin wraps through RhoA-dependent control of membrane growth and in fostering myelin stability via Cdc42-dependent organization of cytoskeletal septins. Together, these findings indicate that IPP-containing Pinch2 is a novel critical cell-autonomous molecular hub ensuring synchronous control of key signaling networks during developmental myelination.

Summary statement

Pinch proteins are core components of a ternary protein complex comprising Ilk and Parvin (IPP). This work identifies Pinch2 as key regulator of the formation and maturation of CNS myelin.
What the flip? What the P-N flip can tell us about proactive suppression
Authors: Tam Joyce , Callahan-Flintoft Chloe , Wyble Brad
Published: March 2022

It has been debated whether salient distractors in visual search can be proactively suppressed to completely prevent attentional capture, as the occurrence of proactive suppression implies that the initial shift of attention is not entirely driven by physical salience. While the presence of a Pd component in the EEG (associated with suppression) without a preceding N2pc component (associated with selection) has been used as evidence for proactive suppression, the link between these ERPs and the underlying mechanisms is not always clear. This is exemplified in two recent papers that observed the same waveform pattern, where an early Pd-like component flipped to a N2pc-like component, but provided very different interpretations (Drisdelle & Eimer, Psychophysiology, 58(9), 1-12, 2021; Kerzel & Burra, Journal of Cognitive Neuroscience, 32(6), 1170-1183, 2020). Using RAGNAROC (Wyble et al., Psychological Review, 127(6), 1163-1198, 2020), a computational model of reflexive attention, we successfully simulated this ERP pattern with minimal changes to its existing architecture, providing a parsimonious and mechanistic explanation for this flip in the EEG that is unique from both of the previous interpretations. Our account supports the occurrence of proactive suppression and demonstrates the benefits of incorporating computational modelling into theory building.
A dynamic framework for sustainable open innovation in the food industry
Authors: Venturelli Andrea , Caputo Andrea , Pizzi Simone , Valenza Giuseppe
Published: March 2022

Purpose

This study aims to take a holistic perspective to investigate how open innovation supports sustainability and the contribution to the Unite Nations (UN) Sustainable Development Goals (SDGs).

Design/methodology/approach

The study is based on an in-depth single case study of Andriani SpA, a leading Italian company in the food industry. The case is built by triangulating data from direct observations, documentary analysis and semi-structured interviews.

Findings

The findings show an organization that has developed its competitive advantage by adopting open innovation to embed sustainability in its strategy and business model. The case study complements the understanding of how open innovation can effectively drive strategic renewal and innovation activities to address sustainability objectives in the food industry.

Originality/value

This study contributes to theoretical development by offering new and insightful explanations of firms' strategic behaviour and coevolution toward sustainability via open innovation. It provides practitioners, policymakers, researchers and students with reflections and inspiration about how open innovation may be deployed to support a holistic strategic renewal aimed at sustainability objectives, such as the SDGs, in the food industry.
Natural resource effect on child health outcomes in a multifactor health production model in developing countries
Authors: Gani Azmat
Published: March 2022

Purpose

This study investigates if wealth from natural resources impacts child health in developing countries.

Design/methodology/approach

The methodology includes testing the effect of rents from natural resources on under-five mortality rates using a multifactor health production model for 57 developing nations. The panel estimation procedure was applied to data covering 2002 to 2017, disaggregated by non-renewable and renewable resources and low and medium human development countries.

Findings

The results provide strong evidence that wealth from total natural resources has not been associated with reductions in under-five mortality rates. However, disaggregation of the sample countries by natural resource constituents revealed that only the wealth of non-renewable is strongly inversely associated with under-five mortality rates. Further disaggregation of countries by the low and medium human development constituents revealed a statistically insignificant negative correlation of non-renewable resources wealth and under-five mortality in the low human development countries. In contrast, the results of the medium human development countries revealed that wealth from natural resources (both non-renewable and renewable) had not been associated with any reductions in under-five mortality rates. The results also confirm that immunization levels, nutrition, private spending on health care, air quality, urban living and countries closer to the equator are other strong correlates of under-five mortality rates in low human development countries.

Social implications

The findings here have implications for the timely achievement of the United Nations Sustainable Development Goal 3 (to reduce under-five deaths to around 25 per 1,000 live births by 2030). Governments ought to ensure that incomes from the extractive sector are aligned in forms that promote and feed into improving child health wellbeing.

Originality/value

This research creates a shift from aggregate health wellbeing research agenda to investigate how specific aspects of human development can be linked to wealth from non-renewable and renewable natural resources in developing nations. It adds new knowledge and provides health and natural resources policymakers opportunities to combine their policies and synergize efforts to improve child health outcomes.
Impact of board attributes on stock liquidity: evidence from Pakistani panel data
Authors: Khan Javed , Rehman Shafiq Ur , Khan Inayat
Published: March 2022

Purpose

This study investigates the impact of board characteristics on the stock liquidity of Pakistani listed non-financial firms for the period 2007–2016.

Design/methodology/approach

The study uses fixed-effects regression model on a sample of 170 non-financial firms listed on the Pakistan Stock Exchange for regressing the impact of board attributes on stock liquidity while for addressing the endogeneity two-stage least-square (2SLS) and lagged structure models are used.

Findings

The study finds that board meetings (BM), directors' attendance (DAT) at BM, board gender diversity, the number of board subcommittees (NBC) and board foreign diversity (BFD) positively affect stock liquidity. Checking the robustness through 2SLS and lagged structure models, it is suggested that the findings are robust to the problem of endogeneity.

Practical implications

Outcomes of the study signify the role of novel board attributes in improving the stock liquidity which has implications for investors, the board of directors and policymakers.

Originality/value

The authors are the first to investigate the impact of novel board attributes–BFD, directors' remuneration (DR), DAT and the number of board sub-committees on stock liquidity. Up to the best of researchers' knowledge, these board attributes have never been examined before in relation to stock liquidity.
Determinants of corporate governance disclosure: evidence from an emerging market
Authors: Ronoowah Rishi Kapoor , Seetanah Boopen
Published: March 2022

Purpose

This study aims to examine the influence of corporate governance (CG) mechanisms and ownership structures on corporate governance disclosure (CGD) in listed Mauritian companies.

Design/methodology/approach

Multivariate regression techniques, both static and dynamic panel data models, were employed to analyse the effect of the determinants on the CGD level of 42 Mauritian listed companies (38 non-financial and four financial firms) from 2009 to 2019.

Findings

In the static model comprising 42 firms, CG attributes such as board size, board meeting frequency, CG committee meeting frequency and audit committee meeting frequency are major determinants of CGD, whereas ownership structure variables such as managerial ownership and institutional ownership do not influence CGD. In the dynamic model, only the CG meeting frequency is a major determinant. The determinants of CGD vary between non-financial and financial firms.

Research limitations/implications

This study is limited to CGD in listed firms, excluding mandatory disclosures and unlisted firms. Future research can use qualitative approaches to better understand CGD behaviour with an extension to mandatory disclosures and non-listed firms.

Practical implications

Policymakers can rely on determinants to draw policy measures to raise CG standards further. Domestic and foreign investors may also depend on the determinants of their expectations of CGD while making investment and credit decisions.

Originality/value

This study contributes to the extant literature by examining a new determinant of CGD: CG committee meeting frequency. It also investigates any differences in the determinants between financial and non-financial firms with different listing status.
Toward the emergence of “humane” entrepreneurial ecosystems. Evidence from different cultural contexts
Authors: Canestrino Rossella , Magliocca Pierpaolo , Ćwiklicki Marek , Pawełek Barbara
Published: March 2022

Purpose

Adopting more sustainable and social-oriented perspectives is crucial for the emergence of the so-called humane entrepreneurial ecosystems (HEEs), the last ones supporting the improvement of both economic, environmental and social wealth. Entrepreneurs act as keystone players in each entrepreneurial ecosystem, thus the emergence of Humane Entrepreneurship (HumEnt) is crucial in shaping HEEs. Given the role of culture in affecting HumEnt, the relationships between Humane Orientation (HO) – as defined in the GLOBE project – and the basic components of Humane Entrepreneurship (HumEnt) were, particularly, explored in a selected sample of countries. Both Intellectual Capital (IC) and knowledge management (KM) perspectives were adopted in pursuing the research goal.

Design/methodology/approach

The study approaches this by the mean of the Ward method with Euclidean squared distance and thek-means method. The GLOBE project, the Global Entrepreneurship Monitor (GEM), the Environmental Performance Index (EPI) and the International Social Survey Program (ISSP) were used as data sources. Correlations between HO “as is” scores and each components of HumEnt were checked for the world sample (N = 36), as well as for the groups of innovation-driven countries (N = 17) and European countries (N = 14).

Findings

Research results show a conditional confirmation of the developed hypotheses, depending on countries cultural levels of HO, with a moderating role exercised by the economic development on the relationship between culture and HumEnt.

Originality/value

Given the increasing pressure of fundamental societal challenges, such as climate change, poverty and increasing inequality within and between countries intensified by pandemic (UN report, 2021), integrating the more traditional approaches to profit seeking with the more sustainable and human-centric perspective is a priority for both scholars and society at large. Previous researches do not provide explanation about the contextual factors responsible for the emergence of more humane-oriented entrepreneurial ecosystems, especially when referring to culture. This article broadens our understanding about the reason why both HumEntr and HEEs differently arise and develop in different cultural contexts.
The influence of Internet shopping and use of credit cards on gender differences in compulsive buying
Authors: Xu Changqin , Unger Alexander , Bi Chongzeng , Papastamatelou Julie , Raab Gerhard
Published: March 2022

Purpose

Buying behavior has been significantly altered by technological developments as a result of the rise of the Internet. Online buying behavior is also inextricably linked to electronic payment systems, such as credit cards. This paper investigates how credit-card systems and online shopping increases compulsive buying of female and male consumers.

Design/methodology/approach

In the current study, the authors tested the influence of credit card possession and the role of Internet shopping on gender differences in compulsive buying in a representative German sample (n = 1,038). Binary logistic regression analysis and moderator analysis were applied.

Findings

As predicted, Internet shopping increased compulsive buying, but the association was the same for females and males. Further, credit card possession moderated the effect of gender on compulsive buying, with females showing a higher proneness to compulsive buying.

Originality/value

This research, which is based on a representative population study, contributes to the understanding of the role of credit cards and the one of online shopping in developing compulsive buying patterns among female and male consumers.
Has COVID-19 pushed digitalisation in SMEs? The role of entrepreneurial orientation
Authors: Penco Lara , Profumo Giorgia , Serravalle Francesca , Viassone Milena
Published: March 2022

Purpose

The authors’ aim is to investigate if entrepreneurial orientation (EO) has a role in interpreting an external crisis, such as COVID-19, as an opportunity for investing in digital transformation.

Design/methodology/approach

The authors undertook multiple case study research on the digital transformation of seven “Made in Italy” SMEs and proposed a conceptual framework that sees an external stimulus (e.g. the pandemic) as a driver of the digitalisation, filtered by the entrepreneurial orientation of SMEs.

Findings

The authors’ results show how EO deals with the changing environment and helps address the market opportunities related to digitalisation.

Research limitations/implications

This study contributes to the existing literature on EO and digital transformation of SMEs, creating a new model for forthcoming studies on this topic. In addition, interesting insights are offered on the role of EO to promote the introduction of digital transformation in SMEs operating in the “Made in Italy” sectors.

Practical implications

This study shows the role of EO as a reactive characteristic during a crisis. Thus, the authors’ suggestion to SMEs is to develop their EO as a part of the strategic orientation. In addition, this work encourages policymakers to invest in the promotion of specific interventions aimed at supporting entrepreneurs in enhancing their capacity to effectively manage digital transformation.

Originality/value

Identifying the most important triggers of digitalisation in times of crisis remains an underexplored area of research. Thus, this study adds value to both digital transformation and entrepreneurial orientation topics.
In search of performance-oriented leadership behaviours in the Ghanaian financial service sector: the role of knowledge sharing
Authors: Kyei-Frimpong Michael , Nyarko Adu Isaac , Suleman Abdul-Razak , Owusu Boakye Kwame
Published: March 2022

Purpose

This study seeks to examine the mediating role of knowledge sharing (KNS) in the nexus between leadership behaviours and organizational performance (OP).

Design/methodology/approach

Using the survey research design, data were obtained from 335 employees in the Ghanaian financial service sector. Responses were analysed using IBM SPSS (v.23.0), Smart PLS 3.0 and Haye’s (2017) PROCESS macro.

Findings

KNS mediated the relationship between leadership behaviours and OP. In addition, transformational leadership behaviour and transactional leadership behaviour positively relate to OP rather than transfor-sactional leadership behaviour.

Practical implications

The findings of this study give credence to the disputed notion that KNS plays a significant role in effective leadership behaviours that enhances OP.

Originality/value

This paper provides a distinctive approach in examining the interrelationship among leadership behaviours, OP and KNS in the Ghanaian financial service sector.
Prioritising optimal underutilised historical buildings for adaptive reuse: a performance-based MCDA framework validation in Auckland, New Zealand
Authors: Aigwi Itohan Esther , Nwadike Amarachukwu Nnadozie , Le An Thi Hoan , Rotimi Funmilayo Ebun , Sorrell Tanya , Jafarzadeh Reza , Rotimi James
Published: March 2022

Purpose

Currently trending as a practical approach to promote urban and seismic resilience, the adaptive reuse of historical buildings relies on expertise from various professional backgrounds ranging from conservation, urban planning, construction management, architecture, engineering to interior design. This paper explores the applicability of a performance-based multiple criteria decision assessment (MCDA) framework to prioritise underutilised historical buildings for adaptive reuse in Auckland, New Zealand while balancing the diverse interest of all relevant stakeholders.

Design/methodology/approach

A focus group workshop was conducted for relevant adaptive stakeholders in Auckland, New Zealand, to test the applicability of the performance-based MCDA framework developed by Aigwiet al.(2020) and prioritise four underutilised historical building alternatives for adaptive reuse interventions in Auckland, New Zealand.

Findings

Findings from this study revealed the significant potentials of the performance-based MCDA framework, both as an evidence-based measurement tool to prioritise underutilised earthquake-prone historical buildings in Auckland's central business district and as an effective decision-making strategy. Also, the framework allowed the inclusion of diverse stakeholders through the integration of collaborative rationality, ensuring consistency and transparency in the decision-making process.

Originality/value

The successful validation of the existing performance-based MCDA framework in Auckland, New Zealand, using multiple historical building alternatives, further strengthens its preceding validation by Aigwiet al.(2019) using only two historical buildings in Whanganui, New Zealand. The findings provide a theoretical platform for urban planning researchers to advance performance-based planning for adaptive reuse to other locations and fields. There are also interesting implications for local councils, heritage agencies, architects, urban planners, policymakers, building owners and developers in Auckland, New Zealand, as a guide to improving their understandings of: (1) the intangible values of optimal historical buildings perceived by the community as worthy of protection through adaptive reuse; and (2) the targeted needs of communities in the new functions of an optimal alternative from a group of representative historical building alternatives.
A lesson in missed opportunities: examining the use of data visualizations in online history lessons
Authors: Finholm Carrie E. , Shreiner Tamara L.
Published: March 2022

Purpose

Over the last several decades, individuals have had access to and encountered more data than ever before. Data can be used to persuade people how to vote, support policies, adopt arguments or agendas and buy products. Data directly relate to our everyday lives including our finances, careers, educational performance and health. Therefore, it is more critical than ever for individuals and students to become data literate. This article presents a study examining the use of data visualizations in K-12 history lessons from eight popular online curricular resources.

Design/methodology/approach

The method employed was content analysis of 1,356 lesson plans across the eight websites.

Findings

About a third of the history lessons reviewed contained data visualizations, but there were mixed results across websites as to whether lesson plans provided guidance on data literacy instruction.

Practical implications

Because online lesson plans frequently miss opportunities to use data visualizations to deepen students’ understanding and support data literacy skills, teachers need to be aware of missed opportunities and consider ways to enhance or revise the lessons.

Originality/value

This study provides insight into the likelihood that history lessons found on popular online curriculum websites will support data literacy instruction. The lack of pedagogical guidance in such curricular resources underscores the importance of including data literacy in teacher education and professional development.
Temporal variations of Microsporidia diversity and discovery of new host–parasite interactions in a lake ecosystem
Authors: Chauvet Marina , Debroas Didier , Moné Anne , Dubuffet Aurore , Lepère Cécile
Published: March 2022

Microsporidia are a large group of obligate intracellular eukaryotic parasites related to Fungi. Recent studies suggest that their diversity has been greatly underestimated and little is known about their hosts other than metazoans, and thus about their impact on the communities at the base of the food web. In this work, we therefore studied the diversity of Microsporidia over one year and identified potential new hosts in small‐sized fractions (<150 μm) in a lake ecosystem using a metabarcoding approach coupled with co‐occurrence networks and tyramide signal amplification‐fluorescent in situ hybridization. Our analysis shows a great Microsporidia diversity (1 472 OTUs), with an important part of this diversity being unknown. Temporal variations of this diversity have been observed, which might follow temporal variations of their potential hosts such as protists and microzooplankton. New hosts among them were identified as well as associations with phytoplankton. Indeed, repeated infections were observed in Kellicottia (rotifers) with a prevalence of 38% (infected individuals). Microsporidia inside a Stentor (ciliate) were also observed. Finally, potential infections of the diatom Asterionella were identified (prevalence <0.1%). The microsporidian host spectrum could be therefore even more important than previously described, and their role in the functioning of lake ecosystems is undoubtedly largely unknown.
Efficacy of plasma exchange therapy for diffuse alveolar hemorrhage in patients with microscopic polyangiitis
Authors: Abe Yoshiyuki , Kusaoi Makio , Tada Kurisu , Yamaji Ken , Tamura Naoto
Published: March 2022

Introduction

Diffuse alveolar hemorrhage (DAH) is associated with high mortality. We examined the efficacy of plasma exchange (PE) therapy for reducing mortality in patients with patients with microscopic polyangiitis (MPA) and DAH.

Methods

In this 52‐week, nonrandomized, open‐label, one‐arm, historical control, double‐center controlled trial, four patients with MPA and DAH admitted to Juntendo University Hospital or Juntendo Koto Geriatric Medical Center between 2018 and 2021 were enrolled. Sixteen patients with MPA and DAH admitted to the two centers between 1998 and 2018 who did not receive PE were included as the historical control group. The primary outcome was the 52‐week survival rate of patients in each treatment arm.

Results

The 52‐week survival rate of patients in the PE group (n = 4) was higher than that of the historical control group (n = 16) (100% vs. 13%, p = 0.04).

Conclusion

We found that PE may be efficacious for reducing mortality in patients with MPA and DAH.
Plasmapheresis for systemic vasculitis
Authors: Fukuoka Kazuhito , Kishimoto Mitsumasa , Kawakami Takahisa , Komagata Yosinori , Kaname Shinya
Published: March 2022

Systemic vasculitides include a variety of, and numerous diseases. In 2012, the International CHAPEL HILL Consensus Conference (CHCC2012) led to a major reorganization of the classification of vasculitis, and this is still in wide use today. Although the results of plasmapheresis for individual diseases have been sometimes shown, there are few systematic reviews that discuss the effects along with vasculitis classification. Therefore, we will discuss the efficacy and the latest evidence for each vasculitis according to the CHCC 2012 classification in this review. This review provides a comprehensive overview of the estimation of plasmapheresis in each of the vasculitides, with a particular focus on small vasculitides, which have recently discussed frequently. For some time now, plasma exchange therapy (PEX) has been frequently used and is expected to be effective in some diseases, most of which are included in small vessel vasculitides. In particular, data showing efficacy have been accumulated for immune complex vasculitis, and the recommendation seems to be high. For instance, anti‐GBM nephritis, concomitant use of PEX is essential and strongly recommended. On the other hand, for ANCA‐related vasculitis among small vessel vasculitis, RCTs have recently shown negative results. In particular, the PEXIVAS trial statistically showed that PEX has no potential to reduce the mortality and renal death in AAV, but the ASFA, ACR, and KDIGO guidelines following this trial all regard PEX as salvage therapy or selective treatment for severe cases. As plasmapheresis is often performed in combination with other therapies, it is difficult to evaluate to clarify its efficacy on its own, and this predisposition may be pronounced in vasculitis, a rare disease. Although statistically significant differences are not apparent, the diseases that show a trend toward efficacy may possibly include treatment‐sensitive subgroups. Further analysis is expected in the future.
Continuously monitored vital signs for detection of myocardial injury in high‐risk patients – An observational study
Authors: Loft Frederik C. , Rasmussen Søren M. , Elvekjaer Mikkel , Haahr‐Raunkjaer Camilla , Sørensen Helge B. D. , Aasvang Eske K. , Meyhoff Christian S. ,   WARD‐Project Group
Published: March 2022

Background

Patients are at risk of myocardial injury after major non‐cardiac surgery and during acute illness. Myocardial injury is associated with mortality, but often asymptomatic and currently detected through intermittent cardiac biomarker screening. This delays diagnosis, where vital signs deviations may serve as a proxy for early signs of myocardial injury. This study aimed to assess the association between continuous monitored vital sign deviations and subsequent myocardial injury following major abdominal cancer surgery and during acute exacerbation of chronic obstructive pulmonary disease.

Methods

Patients undergoing major abdominal cancer surgery or admitted with acute exacerbation of chronic obstructive pulmonary disease had daily troponin measurements. Continuous wireless monitoring of several vital signs was performed for up to 96 h after admission or surgery. The primary exposure was cumulative duration of peripheral oxygen saturation (SpO2) below 85% in the 24 h before the primary outcome of myocardial injury, defined as a new onset ischaemic troponin elevation assessed daily. If no myocardial injury occurred, the primary exposure was based on the first 24 h of measurement.

Results

A total of 662 patients were continuously monitored and 113 (17%) had a myocardial injury. Cumulative duration of SpO2 < 85% was significantly associated with myocardial injury (mean difference 14.2 min [95% confidence interval −4.7 to 33.1 min]; p = .005). Durations of hypoxaemia (SpO2 < 88% and SpO2 < 80%), tachycardia (HR > 110 bpm and HR > 130 bpm) and tachypnoea (RR > 24 min−1 and RR > 30 min−1) were also significantly associated with myocardial injury (p < .04, for all).

Conclusion

Duration of severely low SpO2 detected by continuous wireless monitoring is significantly associated with myocardial injury in high‐risk patients admitted to hospital wards. The effect of early detection and interventions should be assessed next.
Oophorectomy for ovarian torsion – should this be abandoned?
Authors: Soh Pei Qian , Cheng Claudia , Reddington Charlotte , Dior Uri P. , Healey Martin
Published: March 2022

Background

Management of ovarian torsion ranges from de‐torsion to oophorectomy and is dependent on various factors. Oophorectomy can have significant implications for fertility and general health, thus requiring careful consideration.

Aims

We evaluate the management of ovarian torsion at a tertiary hospital over a ten‐year period and identify the predictors of oophorectomy in ovarian torsion cases.

Materials and methods

Inpatient notes of patients who underwent surgical management for acute ovarian torsion at a tertiary hospital in Victoria, Australia, were reviewed, from January 2008 to June 2018. We reported the incidence and predictors of oophorectomy and ovarian ischaemia and current practices in oophoropexy.

Results

Our analysis included 159 patients. The incidence of oophorectomy was 47%. After confounders were adjusted, increasing age was the only significant predictor for oophorectomy. The adjusted odds ratio of having an oophorectomy based on age alone was 1.10 for each year increase in age between the ages of 15 and 68 (P = 0.001, 95% confidence interval 1.04–1.16). Of those with oophorectomy, 57% had ischaemia confirmed histologically. There were no significant predictors for ischaemia.

Conclusion

The incidence of oophorectomy in this audit is comparable to reported incidences in current literature. However, with increasing evidence to support ongoing ovarian function even in cases where ischaemia is histologically confirmed, this incidence could be lowered. Age was the only variable that was found to have a significant effect on the incidence of oophorectomy.
Persistence of treatment in patients with ulcerative colitis who responded to tofacitinib therapy: data from the open‐label, long‐term extension study, OCTAVE open
Authors: Panaccione Remo , Abreu Maria T. , Lazariciu Irina , Mundayat Rajiv , Lawendy Nervin , Salese Leonardo , Woolcott John C. , Sands Bruce E. , Chaparro María
Published: March 2022

Background

Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC).

Aim

This post hoc analysis evaluated tofacitinib persistence in patients with UC in OCTAVE Open, an open‐label, long‐term extension study of patients receiving tofacitinib 5 or 10 mg twice daily.

Methods

Kaplan‐Meier estimates for tofacitinib drug survival and reasons for discontinuations were evaluated. Baseline factors were analysed as predictors of persistence.

Results

This analysis included 603 patients: 280 entered OCTAVE Open with a clinical response (164 in remission and 116 not in remission), 220 were delayed responders, 75 were retreatment responders and 35 were dose escalation responders, treated for up to 7 years in OCTAVE Open. Of these, 118 (42.1%) responders, 121 (55.0%) delayed responders, 40 (53.3%) retreatment responders and 17 (48.6%) dose escalation responders discontinued tofacitinib with a median time to discontinuation of 5.6, 4.5, 4.0 and 4.4 years, respectively. The estimated 2‐ and 5‐year drug survival rates in the responders (including patients in remission and not in remission) were 73.9% and 54.5%, respectively. Corresponding persistence values for delayed responders were 69.5% and 45.2%, for retreatment responders, 70.7% and 40.0%, and for dose escalation responders, 74.3% and 32.8%.

Conclusion

In OCTAVE Open, a high proportion of patients maintained tofacitinib treatment, with the median survival by group ranging from 4.0 to 5.6 years although these analyses are post hoc and limited by sample size. Further research should focus on factors to enhance persistence with tofacitinib treatment in patients with UC.
Leptin gene contributes to beef marbling standard, meat brightness, meat firmness, and beef fat standard of the Kumamoto sub‐breed of Japanese Brown cattle
Authors: Matsumoto Hirokazu , Kimura Satoshi , Nagai Yohsuke , Fukuda Yuta , Miyazaki Kunio , Imai Saki , Inenaga Toshiaki , Kashimura Atsushi
Published: March 2022

The Kumamoto sub‐breed of Japanese Brown cattle has unique characteristics, such as great growth rate, and their contribution as future breeding materials is expected. To develop a DNA marker for their breeding, we investigated the effects of Leptin gene, controlling energy homeostasis, on carcass traits of the Kumamoto sub‐breed. Sequence comparison identified five single nucleotide polymorphisms (SNPs): four linked synonymous mutations and one nonsynonymous mutation. Statistical analysis revealed that c.239C > T (p.A80V) had significant effects on the traits related with quality grade: beef marbling standard (p = 0.0132), meat brightness (p = 0.0383), and meat firmness (p = 0.0115). The C allele showed favorable effects; these scores of the C/C cattle were significantly higher than those of the C/T cattle. On the other hand, the effect of c.399T > C was observed on meat firmness (p = 0.0172) and beef fat standards (BFS) (p = 0.0129). The C/C cattle showed higher values of these traits than the T/T cattle. Our data suggested that these SNPs in Leptin gene could be used as a DNA marker for breeding of the Kumamoto sub‐breed.
Comparative effects of low‐carbohydrate, full‐strength and low‐alcohol beer on gastric emptying, alcohol absorption, glycaemia and insulinaemia in health
Authors: Stevens Julie E. , Jalleh Ryan J. , Trahair Laurence G. , Marathe Chinmay S. , Horowitz Michael , Jones Karen L.
Published: March 2022

Aims

The aim of this study was to evaluate the comparative effects of low‐carbohydrate (LC), full‐strength (FS), and low‐alcohol (LA) beer on gastric emptying (GE), ethanol absorption, glycaemia and insulinaemia in health.

Methods

Eight subjects (four male, four female; age: 20.4 ± 0.4 years; BMI 22.7 ± 0.4 kg/m2) had concurrent measurements of GE, plasma ethanol, blood glucose and plasma insulin for 180 min on three separate occasions after ingesting 600 mL of (i) FS beer (5.0% w/v, 246 kcal, 19.2 g carbohydrate), (ii) LC beer (4.6% w/v, 180 kcal, 5.4 g carbohydrate) and (iii) LA beer (2.6% w/v, 162 kcal, 17.4 g carbohydrate) labelled with 20 MBq 99mTc‐calcium phytate, in random order.

Results

There was no difference in the gastric 50% emptying time (T50) (FS: 89.0 ± 13.5 min vs LC: 79.5 ± 12.9 min vs LA: 74.6 ± 12.4 min; P = .39). Plasma ethanol was less after LA than LC (P < .001) and FS (P < .001), with no difference between LC and FS (P = 1.0). There was an inverse relationship between plasma ethanol at 15 min and GE after LA (r = −0.87, P < .01) and a trend for inverse relationships after LC (r = −0.67, P = .07) and FS (r = −0.69, P = .06). The AUC 0–180 min for blood glucose was greater for LA than LC (P < .001), with no difference between LA and FS (P = .40) or LC and FS (P = 1.0).

Conclusion

In healthy young subjects, GE of FS, LC and LA beer is comparable and a determinant of the plasma ethanol response.
Evaluating Treatment Effects in Group Sequential Multivariate Longitudinal Studies with Covariate Adjustment
Authors: Jeffries Neal O. , Troendle James F. , Geller Nancy L.
Published: March 2022

Jeffries et al. (2018) investigated testing for a treatment difference in the setting of a randomized clinical trial with a single outcome measured longitudinally over a series of common follow-up times while adjusting for covariates. That paper examined the null hypothesis of no difference at any follow-up time versus the alternative of a difference for at least one follow-up time. We extend those results here by considering multivariate outcome measurements, where each individual outcome is examined at common follow-up times. We consider the case where there is interest in first testing for a treatment difference in a global function of the outcomes (e.g., weighted average or sum) with subsequent interest in examining the individual outcomes, should the global function show a treatment difference. Testing is conducted for each follow-up time and may be performed in the setting of a group sequential trial. Testing procedures are developed to determine follow-up times for which a global treatment difference exists and which individual combinations of outcome and follow-up time show evidence of a difference while controlling for multiplicity in outcomes, follow-up, and interim analyses. These approaches are examined in a study evaluating the effects of tissue plasminogen activator on longitudinally obtained stroke severity measurements.
A novel homozygous variant in COX5A causes an attenuated phenotype with failure to thrive, lactic acidosis, hypoglycemia, and short stature
Authors: Torraco Alessandra , Morlino Silvia , Rizza Teresa , Di Nottia Michela , Bottaro Giorgia , Bisceglia Luigi , Montanari Arianna , Cappa Marco , Castori Marco , Bertini Enrico , Carrozzo Rosalba
Published: March 2022

Genetic defect in the nuclear encoded subunits of cytochrome c oxidase are very rare. To date, most deleterious variants affect the mitochondrially encoded subunits of complex IV and the nuclear genes encoded for assembly factors. A biallelic pathogenic variant in the mitochondrial complex IV subunit COX5A was previously reported in a couple of sibs with failure to thrive, lactic acidosis and pulmonary hypertension and a lethal phenotype. Here, we describe a second family with a 11‐year‐old girl presenting with failure to thrive, lactic acidosis, hypoglycemia and short stature. Clinical exome revealed the homozygous missense variant c.266 T > G in COX5A, which produces a drop of the corresponding protein and a reduction of the COX activity. Compared to the previous observation, this girl showed an attenuated metabolic derangement without involvement of the cardiovascular system and neurodevelopment. Our observation confirms that COX5A recessive variants may cause mitochondrial disease and expands the associated phenotype to less severe presentations.
Inflammation on bronchoalveolar lavage cytology is associated with decreased chronic lung allograft dysfunction‐free survival
Authors: Greenland Nancy Y. , Deiter Fred , Calabrese Daniel R. , Hays Steven R. , Kukreja Jasleen , Leard Lorriana E. , Kolaitis Nicholas A. , Golden Jeffrey A. , Singer Jonathan P. , Greenland John R.
Published: March 2022

Background

Lung transplant recipients undergo bronchoalveolar lavage (BAL) to detect antecedents of chronic lung allograft dysfunction (CLAD), but routine assessment of BAL cytology is controversial. We hypothesized that inflammation on BAL cytology would predict CLAD‐free survival.

Methods

In a single‐center retrospective cohort, associations between cytology results and clinical characteristics were compared using generalized‐estimating equation‐adjusted regression. The association between BAL inflammation and CLAD or death risk was assessed using time‐dependent Cox models.

Results

 In 3365 cytology reports from 451 subjects, inflammation was the most common finding (6.2%, 210 cases), followed by fungal forms (5.3%, 178 cases, including 24 cases of suspected Aspergillus). Inflammation on BAL cytology was more common in procedures for symptoms (8.5%) versus surveillance (3.2%,p < .001). Inflammation on cytology was associated with automated neutrophil and lymphocyte counts, acute cellular rejection, infection, and portended a 2.2‐fold hazard ratio (CI 1.2–4.0,p = .007) for CLAD or death. However, inflammation by cytology did not inform CLAD‐free survival risk beyond automated BAL cell counts (p = .57).

Conclusions

Inflammation on BAL cytology is clinically significant, suggesting acute rejection or infection and increased risk of CLAD or death. However, other indicators of allograft inflammation can substitute for much of the information provided by BAL cytology.
S1 Guideline: Diagnosis and therapy of vitiligo
Authors: Böhm Markus , Schunter Jo Ana , Fritz Klaus , Salavastru Carmen , Dargatz Sonja , Augustin Matthias , Tanew Adrian
Published: March 2022

Vitiligo is a common skin disorder characterized by immune‐mediated destruction of melanocytes. Non‐segmental vitiligo, the most common clinical subtype, has usually a chronic course and often results in significant psychosocial consequences for the affected patient. Early recognition, awareness of comorbidity, precise assessment of disease extent and activity, evaluation of impairment of quality of life as well as rapid initiation of treatment based on currently available evidence‐based therapies are crucial cornerstones in the management of vitiligo. This S1 guideline helps German dermatologists to better diagnose and treat vitiligo.
Epidemiology of skin diseases in Germany: systematic review of the current state of research – part 1: cutaneous tumor diseases
Authors: Hansen Inga , Augustin Matthias , Schäfer Ines , Mohr Nicole
Published: March 2022

Epidemiological data are of great importance for the identification of health care needs, the detection of gaps in care, the development of targeted prevention measures, and for the optimization of resource allocation. The aim of this work was to systematically collect all previously published population‐based epidemiological data on skin diseases in Germany. The present part 1 of the publication series deals with tumor diseases of the skin. The results on non‐infectious (part 2) and infectious skin diseases (part 3) form the other parts of this publication series.

A systematic search of the literature spanning the last 15 years was conducted using the PubMed/MEDLINE database. With the aim of including all dermatologic diseases, a diagnostic list was developed based on the ICD‐11 catalogue. This list included 1,347 skin diseases and formed the basis for the search. The literature search yielded 4,650 publications. After two‐stage screening, 72 studies on 43 different skin diseases were included in the synthesis. Among them were 30 publications on cutaneous tumor diseases, the majority was related to malignant melanoma.

This work is the first systematic literature review that aimed to report all available epidemiological data on skin diseases in Germany. In terms of study characteristics, a high heterogeneity was found for the different skin diseases. Even though the methodology of the included epidemiological studies varied considerably, the usefulness of these epidemiological data is extremely wide‐ranging. Thus, this work can serve as a reference for various epidemiological questions.
White matter alterations in familial cortical myoclonic tremor with epilepsy type 1
Authors: Wang Bo , Wang Haotian , Cen Zhidong , Yuan Jiachen , Yang Dehao , Chen Xinhui , Xie Fei , Wang Lebo , Wu Sheng , Ouyang Zhiyuan , Zang Yu‐Feng , Luo Wei
Published: March 2022

Objective

Although previous imaging studies have reported cerebellar gray matter loss in patients with familial cortical myoclonic tremor with epilepsy (FCMTE), the corresponding white matter alterations remain unknown. We investigated white matter structural changes in FCMTE1 and compared them with clinical and electrophysiological features.

Methods

We enrolled 36 patients carrying heterozygous pathogenic intronic pentanucleotide insertions in the SAMD12 gene and 52 age‐ and sex‐matched healthy controls. Diffusion tensor imaging‐derived metrics, including fractional anisotropy, mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were calculated along with white matter voxel‐based morphometry (VBM) analysis. We also examined correlations between magnetic resonance metrics and clinical and electrophysiological features.

Results

We detected widespread white matter reductions in MD, RD, and AD values in FCMTE1 patients, including in the commissural, projection, and association fibers. VBM analysis revealed that increases in white matter volume predominantly occurred in the right cerebellum and sagittal stratum. MD, RD, AD, and VBM analysis clearly indicated changes in the sagittal stratum. We found a positive correlation between VBM values in the right cerebellum and somatosensory‐evoked potential P25–N33 amplitude. Decreased MD and AD values in the right sagittal stratum were detected in patients with versus without photophobia.

Significance

FCMTE is a network disorder involving a wide range of cortical and subcortical structures, including the cerebellum, thalamus, thalamocortical connections, and corticocortical connections. The right sagittal stratum is closely related with visual symptoms, especially photophobia. Our findings indicate that cerebellum and cortical hyperexcitability are closely linked, and emphasize the important role of the cerebellum in the pathophysiological mechanisms of cortical tremor.