bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of institutional logics on vaccine development, production and distribution in Africa
Authors: Chawana Richard , Mamabolo Anastacia , Apostoleris Evangelos
Published: June 2024

Purpose

Africa has the most deaths from infections yet lacks adequate capacity to engage in vaccine development, production and distribution, the cornerstone of efficiently managing and eliminating several infectious diseases. Research has scarcely explored the role of institutional logics in vaccine development, production and distribution, collectively known as end-to-end vaccine manufacturing. This study aims to explore how institutional logics influence firms to engage in the vaccine manufacturing value chain in Africa.

Design/methodology/approach

We conducted multiple case study research using five vaccine manufacturing firms from four African countries in three regions. Qualitative interviews were conducted among 18 executives in 5 vaccine manufacturing firms.

Findings

We identified that the state, corporate and market institutional logics disparately influence the different parts of the vaccine manufacturing value chain. These institutional logics co-exist in a constellation that also shapes the organizational forms. Their constellation has dominant logics that guide behavior, while subdominant and subordinate logics influence behavior to a limited extent. The findings show that institutional logics are a function of contextual factors, such as historical events, technological changes and pandemics.

Originality/value

The study developed a typology that identifies vaccine manufacturing firm archetypes, institutional logics and their constellations underpinned by contextual factors. The findings have implications for firms and policymakers, as they may guide the end-to-end vaccine manufacturing interventions adapted for their regions.
Are resources and demands from accountability policies productive? How leaders build district capacity in response to school turnaround policy
Authors: Torres A. Chris
Published: June 2024

Purpose

As school districts evolve in their ability to actively support schools and educators, they must simultaneously contend with external policies that create additional demands on time and resources. This includes accountability policies aimed at increasing district and school capacity. This study uses Malen and Rice’s (2004) dual dimensions of capacity building to look at how district and charter leaders responded to the demands of Michigan’s Partnership Model, a district-based approach to school turnaround, focusing on how they tried to build capacity in response to the policy and whether and why these capacity building approaches were perceived as productive.

Design/methodology/approach

Semi-structured interviews were conducted with 22 out of 29 Partnership leaders between October 2019 to March 2020 in the second year of policy implementation. Data were analyzed using a combination of index-coding and thematic analysis.

Findings

Most leaders perceived the resources associated with the reform as useful, but the productivity of capacity building efforts was limited because some resources were not adequately matched to what they perceived as a core problem: the recruitment and retention of teachers. Engagement with the reform resulted in building informational and social capital because it fostered collaboration and continuous improvement processes, but leaders perceived technical partnerships as more productive than community partnerships.

Originality/value

Turnaround reforms like the Partnership Model that increase resources for districts and schools likely offer a better chance at success than those that simply focus on accountability threats without accompanying support because they give leaders new opportunities to coordinate and align resources, processes and ideas.
Is knowledge liberating? The role of knowledge behaviors and competition on the workplace happiness of healthcare professionals
Authors: Gonçalves Tiago , Muñoz-Pascual Lucía , Curado Carla
Published: June 2024

Purpose

The purpose of this paper is to highlight the joint impact of competitive culture and knowledge behaviors (sharing, hoarding and hiding) on workplace happiness among healthcare professionals. It addresses a literature gap that critiques the development of happiness programs in healthcare that overlook organizational, social and economic dynamics. The study is based on the Social Exchange Theory, the Conservation of Resources Theory and the principles of Positive Psychology.

Design/methodology/approach

The study analyzes a linear relationship between variables using a structural equation model and a partial least squares approach. The data are sourced from a survey of 253 healthcare professionals from Portuguese healthcare organizations.

Findings

The data obtained from the model illustrate a positive correlation between competitive culture and knowledge hoarding as well as knowledge hiding. Interestingly, a competitive culture also fosters workplace happiness among healthcare professionals. The complex relationship between knowledge behaviors becomes evident since both knowledge hoarding and sharing positively affected these professionals’ workplace happiness. However, no direct impact was found between knowledge hiding and workplace happiness, suggesting that it negatively mediates other variables.

Originality/value

This research addresses a previously identified threefold gap. First, it delves into the pressing need to comprehend behaviors that enhance healthcare professionals’ workplace satisfaction. Second, it advances studies by empirically examining the varied impacts of knowledge hiding, hoarding and sharing. Finally, it sheds light on the repercussions of knowledge behaviors within an under-explored context – healthcare organizations.
CEO reflections on leadership lessons from the global pandemic: back to basics during crisis
Authors: Longenecker Clinton O. , Wittmer Jenell
Published: June 2024

Purpose

The current study qualitatively examined the challenges and lessons learned from Chief Executive Officers (CEOs) during the COVID-19 pandemic. The current study draws upon previous crisis leadership research to understand and classify the most important lessons learned from CEOs.

Design/methodology/approach

A total of 30 in-depth, structured CEO interviews were conducted with large, multi-divisional organizations across market sectors that included healthcare, automotive, steel, agriculture, logistics, distribution, banking, financial services, light manufacturing and industrial services during the COVID-19 pandemic. Three separate judges performed a content analysis, and three main themes (eleven overall lessons) emerged related to high-level leadership lessons learned through the pandemic.

Findings

The leadership lessons that emerged overwhelmingly focused on the importance of emphasizing leadership fundamentals during crisis. CEO’s shared the importance of getting “back to basics” during the pandemic. The current study presents these leadership lessons, along with insights for leadership practices and development, as well as future research. Additionally, questions for reflection are posed to stimulate current and future leaders’ growth and development.

Originality/value

The COVID-19 pandemic has impacted leadership and organizations in an unprecedented manner. Previous research has outlined the leadership traits and behaviors needed to successfully lead through organizational crises. However, little research has examined CEO level lessons learned, focusing on learning from such crises.
Coerced motherhood behind bars: Public support for abortion access for incarcerated women
Authors: Smith Paula , Cullen Francis T. , Pickett Justin T. , Jonson Cheryl Lero
Published: June 2024

Research Summary

The U.S. Supreme Court's Dobbs decision overturning Roe v. Wade has profound implications for the 58,000 incarcerated women who are pregnant. Especially in states that now ban abortion, women in prisons and jails who prefer to terminate their pregnancy will be denied that choice by the government and will be forced to give birth. Based on a July 2023 YouGov survey (N = 800) employing three experiments and measuring attitudes toward inmate abortion and parental aid, the current study examines public opinion on coerced motherhood, focusing on states prohibiting reproductive choice. The results reveal that a majority of the American public favors providing incarcerated women in these states with access to abortion through surgical procedures or medication (pills). Among respondents residing in states banning abortion, more endorse than oppose reproductive rights. Support for abortion is particularly high when the pregnancy is due to rape or poses a risk to a woman's health. Respondents also approve incarcerated mothers receiving parental aid (e.g., baby food, baby clothing, nursery care). Notably, conservative Republicans are most in favor of coercing motherhood and least in favor of providing parental aid.

Policy Implications

Coerced motherhood behind bars is a human rights violation. Our study shows that it is also opposed by the American public. Thus, ideological space exists for reforms aimed at providing incarcerated women with access to reproductive services. Every correctional facility should be given a written protocol (Model Reproductive Services Code) that mandates pregnancy screenings, counseling, and assistance in scheduling services, as well as transportation for surgery and/or access to pills for a medical abortion. Above all, transparency is needed to raise consciousness about coerced motherhood behind bars and to shed light on how corrections professionals handle inmate pregnancies.
Politics and race in the workplace: Understanding how and when trump‐supporting managers hinder black employees from thriving at work
Authors: Rice Darryl B. , Young Nicole C. J. , Taylor Regina M. , Leonard Stephanie R.
Published: June 2024

Our research contributes to the human resource management (HRM) literature that explains the adverse impact of right‐wing populism on workplace diversity, equity, and inclusion (DEI). Accordingly, our study adds to the growing literature that examines the Trump effect on workplace dynamics. To this end, we rely on social information processing theory to argue that managers perceived to be Trump‐supporting, compared to managers perceived to be Trump‐opposing, are less likely to demonstrate inclusive leadership toward Black employees. This decreased demonstration of inclusive leadership is a salient workplace cue for Black employees that they are in an organization where Black employees' thriving at work is undesirable. We also argue this will be especially the case for relatively younger Black employees compared to relatively older Black employees. Across three studies, we find support for our hypotheses. Theoretical and practical implications are discussed.
Witness Seminar: Writing to Politicians
Authors: Kowol Kit , Toye Richard
Published: June 2024

This article represents the transcript of a 2022 witness seminar on the theme of members of the British public writing to politicians. Collectively, the witnesses have experience of this issue dating from the early 1970s through to the present day. Angie Williams shares her experience of handling correspondence for Ed Miliband and Jeremy Corbyn as leaders of the Labour Party. Lord Kinnock (Neil Kinnock) describes what it was like to receive correspondence both as an MP and as Labour Party leader. David Beckingham relates his experience working in the Number 10 Political Office under Theresa May and Boris Johnson. Lord Parkinson (Stephen Parkinson) also gives a perspective on May, for whom he worked both at the Home Office and in Downing Street. Camilla Jequier explains her role dealing with correspondence for two Conservative MPs. The issues explored include attempts to use correspondence to measure public opinion, the shift from letters to email, gifts enclosed with letters, correspondents with mental health issues, death threats, and the emotional dimensions of correspondence. The witnesses had similar or overlapping experiences. There was agreement that correspondence is often misdirected or phrased in ways that are unlikely to be productive. This may point to a failure of citizenship education.
Novel molecular, structural and clinical findings in an Italian cohort of congenital cataract
Authors: Lecca Mauro , Mauri Lucia , Gana Simone , Del Longo Alessandra , Morelli Federica , Nicotra Roberta , Plumari Massimo , Galli Jessica , Sirchia Fabio , Valente Enza Maria , Cavallari Ugo , Mazza Marco , Signorini Sabrina , Errichiello Edoardo
Published: June 2024

The current genetic diagnostic workup of congenital cataract (CC) is mainly based on NGS panels, whereas exome sequencing (ES) has occasionally been employed. In this multicentre study, we investigated by ES the detection yield, mutational spectrum and genotype–phenotype correlations in a CC cohort recruited between 2020 and mid‐2022. The cohort consisted of 67 affected individuals from 51 unrelated families and included both non‐syndromic (75%) and syndromic (25%) phenotypes, with extra‐CC ocular/visual features present in both groups (48% and 76%, respectively). The functional effect of variants was predicted by 3D modelling and hydropathy properties changes. Variant clustering was used for the in‐depth assessment of genotype–phenotype correlations. A diagnostic (pathogenic or likely pathogenic) variant was identified in 19 out of 51 probands/families (~37%). In a further 14 probands/families a candidate variant was identified: in 12 families a VUS was detected, of which 9 were considered plausibly pathogenic (i.e., 4 or 5 points according to ACMG criteria), while in 2 probands ES identified a single variant in an autosomal recessive gene associated with CC. Eighteen probands/families, manifesting primarily non‐syndromic CC (15/18, 83%), remained unsolved. The identified variants (8 P, 12 LP, 10 VUS‐PP, and 5 VUS), half of which were unreported in the literature, affected five functional categories of genes involved in transcription/splicing, lens formation/homeostasis (i.e., crystallin genes), membrane signalling, cell–cell interaction, and immune response. A phenotype‐specific variant clustering was observed in four genes (KIF1A, MAF, PAX6, SPTAN1), whereas variable expressivity and potential phenotypic expansion in two (BCOR, NHS) and five genes (CWC27, KIF1A, IFIH1, PAX6, SPTAN1), respectively. Finally, ES allowed to detect variants in six genes not commonly included in commercial CC panels. These findings broaden the genotype–phenotype correlations in one of the largest CC cohorts tested by ES, providing novel insights into the underlying pathogenetic mechanisms and emphasising the power of ES as first‐tier test.
ProtEGOnist: Visual Analysis of Interactions in Small World Networks Using Ego‐graphs
Authors: Brich N. , Harbig T.A. , Paz M. Witte , Nieselt K. , Krone M.
Published: June 2024

Visualizing small‐world networks such as protein‐protein interaction networks or social networks often leads to visual clutter and limited interpretability. To overcome these problems, we presentProtEGOnist, a visualization approach designed to explore small‐world networks.ProtEGOnistvisualizes networks using ego‐graphs that represent local neighborhoods. Ego‐graphs are visualized in an aggregated state as a glyph where the size encodes the size of the neighborhood and in a detailed version where the original network nodes can be explored. The ego‐graphs are arranged in an ego‐graph network, where edges encode similarity using the Jaccard index. Our design aims to reduce visual complexity and clutter while enabling detailed exploration and facilitating the discovery of meaningful patterns. To achieve this, our approach offers a network overview using ego‐graphs, a radar chart for a one‐to‐many ego‐graph comparison and meta‐data integration, and detailed ego‐graph subnetworks for interactive exploration. We demonstrate the applicability of our approach on a co‐author network and two different protein‐protein interaction networks. A web‐based prototype ofProtEGOnistcan be accessed online athttps://protegonist-tuevis.cs.uni-tuebingen.de/.
Exploring the Design Space of BioFabric Visualization for Multivariate Network Analysis
Authors: Fuchs J. , Dennig F. L. , Heinle M.‐V. , Keim D. A. , Di Bartolomeo S.
Published: June 2024

The visual analysis of multivariate network data is a common yet difficult task in many domains. The major challenge is to visualize the network's topology and additional attributes for entities and their connections. Although node‐link diagrams and adjacency matrices are widespread, they have inherent limitations. Node‐link diagrams struggle to scale effectively, while adjacency matrices can fail to represent network topologies clearly. In this paper, we delve into the design space of BioFabric, which aligns entities along rows and relationships along columns, providing a way to encapsulate multiple attributes for both. We explore how we can leverage the unique opportunities offered by BioFabric's design space to visualize multivariate network data — focusing on three main categories: juxtaposed visualizations, embedded on‐node and on‐edge encoding, and transformed node and edge encoding. We complement our exploration with a quantitative assessment comparing BioFabric to adjacency matrices. We postulate that the expansive design possibilities introduced in BioFabric network visualization have the potential for the visualization of multivariate data, and we advocate for further evaluation of the associated design space. Our supplemental material is available on osf.io.
GBP1 promotes cutaneous squamous cell carcinoma proliferation and invasion through activation of STAT3 by SP1
Authors: Yu Site , Li Yun , Feng Wenjie , Zeng Jizhang , Cui Xu , Zhou Situo , Zhang Pihong
Published: June 2024

Cutaneous squamous cell carcinoma (cSCC) ranks as the second most prevalent skin tumour (excluding melanoma). However, the molecular mechanisms driving cSCC progression remain elusive. This study aimed to investigate GBP1 expression in cSCC and elucidate its potential molecular mechanisms underlying cSCC development. GBP1 expression was assessed across public databases, cell lines and tissue samples. Various assays, including clone formation, CCK8 and EdU were employed to evaluate cell proliferation, while wound healing and transwell assays determined cell migration and invasion. Subcutaneous tumour assays were conducted to assess in vivo tumour proliferation, and molecular mechanisms were explored through western blotting, immunofluorescence and immunoprecipitation. Results identified GBP1 as an oncogene in cSCC, with elevated expression in both tumour tissues and cells, strongly correlating with tumour stage and grade. In vitro and in vivo investigations revealed that increased GBP1 expression significantly enhanced cSCC cell proliferation, migration and invasion. Mechanistically, GBP1 interaction with SP1 promoted STAT3 activation, contributing to malignant behaviours. In conclusion, the study highlights the crucial role of the GBP1/SP1/STAT3 signalling axis in regulating tumour progression in cSCC. These findings provide valuable insights into the molecular mechanisms of cSCC development and offer potential therapeutic targets for interventions against cSCC.
Shedding light on overlooked pollinators: Global insights into floral interactions of velvet ants (Hymenoptera: Mutillidae and Myrmosidae)
Authors: Parejo‐Pulido Daniel , Díaz‐Calafat Joan , Robla Jairo
Published: June 2024

Plant–animal interactions constitute a recurrent and central focus in ecological research, with pollination representing one of its most extensively studied aspects. While certain insect orders have traditionally received considerable attention due to their abundance as flower visitors and their efficiency in pollination, it is undeniable that the significance of other less popular and neglected flower visitors cannot be overlooked. In this regard, velvet ants (Hymenoptera: Mutillidae and Myrmosidae) constitute an excellent study model, as the knowledge of their ecology (e.g., their feeding preferences) is still very limited despite being reported as common flower visitors. In this study, we conducted a comprehensive global review of velvet ant floral visitation patterns using citizen science data, literature records and unpublished data. We used network metrics to explore their flower‐visit preferences on a global scale, as well as depending on the bioregion where the interaction was recorded and the sex of the velvet ants. In addition, we explored their potential role as pollen vectors examining the number of photographic records where velvet ants had pollen attached to their bodies. Our analyses revealed that velvet ants are generalist flower visitors of a wide range of plant families, with Apiaceae, Asteraceae, Euphorbiaceae, Rhamnaceae and Fabaceae as the most visited. Despite differences in flowering plant and velvet ant composition across bioregions causing differences in plant‐velvet ant interactions, velvet ants visited flowering plants in a generalistic way across the globe. Males and females seemed to visit different plant communities, with males being more generalist than females. Furthermore, 42.7% (likely an underestimation) of the photographic records of velvet ants visiting flowers showed pollen attached to their bodies in the same way as in other pollinating insects, suggesting the same potential role as pollinators. There remains ample scope for ongoing investigation to comprehensively assess the importance of numerous arthropods, including velvet ants, not only as flower visitors but also as potential pollinators.
Impact of salivary flow inhibition on masticatory behaviours in healthy individuals
Authors: Goto Rie , Ochiai Yuto , Takei Eri , Ita Reiko , Ono Kazhihiro , Takei Ryo , Washio Hideaki , Takahashi Hajime , Tsujimura Takanori , Magara Jin , Inoue Makoto
Published: June 2024

Background

It remains unclear how the salivary flow and the fat content of food affect bolus formation during mastication.

Objectives

We aimed to clarify: (1) how hyposalivation affects jaw‐closing and hyoid‐elevating muscle activities in bolus formation, and (2) if the effect of hyposalivation on muscle activity depends on the fat content of food.

Methods

Eighteen healthy male volunteers were instructed to freely ingest four test foods: Plain, Fat without seasoning, Fat with seasoning, and Soft rice crackers. Masseter and suprahyoid electromyographic activities were recorded before and 30 min after the administration of atropine sulfate, a muscarinic receptor antagonist that induces hyposalivation.

Results

Hyposalivation extended the masticatory duration significantly in all the test foods except Fat with seasoning. Masticatory cycle time was significantly longer with vs without hyposalivation for the Soft (p = .011). Suprahyoid activity/cycle was significantly greater with vs without hyposalivation (p = .013). Masticatory cycle time was significantly longer at the late stage with vs without hyposalivation for the Soft (p < .001). Suprahyoid activity/cycle was significantly greater at the middle (p = .045) and late stages (p = .002) with vs without hyposalivation for the Soft and greater at the late stage with vs without hyposalivation for the Plain (p = .043). Changes in masticatory cycle time and suprahyoid activity/cycle for these foods had significantly positive relationship (p < .001).

Conclusion

Hyposalivation‐induced changes in masticatory behaviours resulted from the middle and late stage suprahyoid activity. Fat content and seasoning compensate for salivary flow inhibition.
New insights into the regulation of ethylene biosynthesis during leaf senescence in Arabidopsis
Authors: Mei Yuanyuan , Wang Ning Ning
Published: June 2024

This article is a Commentary on Zhu et al. (2024), 244: 116–130.
You can't always get what you want from pollinators
Authors: Burd Martin
Published: June 2024

This article is a Commentary on Duncan et al. (2024), 244: 307–317.
Multi‐level governance in higher education quality assurance: Agencification and policy coordination in Spain
Authors: García‐Juanatey Ana , Jordana Jacint , Sancho David
Published: June 2024

This article aims to examine the emergence of a system of multi‐level governance in Higher Education quality assurance during recent decades in Spain, as a particular case within the European Space of Higher Education. Although there is a well‐established multi‐level structure in the governance of this area at the European level, it is not very common to find countries having an internal multi‐level configuration. Most countries have allocated quality assurance at the national level, either concentrating responsibilities into a single agency or allowing competition between accreditation bodies. Thus, the Spanish scenario stands out as very singular model for the governance of Higher Education quality assurance, deserving attention to comprehend the intricacies of its coordination. Here we examine its development over the last two decades, and discuss three factors that have shaped inter‐agencies' relations: first, the sequence of agency creation and their accumulated expertise; second, the role of institutional structures for multi‐level coordination; and third, informal practices related to inter‐governmental relations, and the influence of country administrative traditions. From discussing this case, this article identifies three key lessons for understanding agency relations in multilevel governance environments: first, path dependence significantly impacts‐regulatory interactions over time; second, the Administrative culture, particularly centralist traditions, considerably shapes relationships in multi‐level bodies; and, third, the coordination models in regulatory networks (hierarchical, network or market‐based) tend to reflect those underlying political dynamics.
The prevention of congenital toxoplasmosis using a combination of Spiramycin and Cotrimoxazole: The long‐time experience of a tertiary referral centre
Authors: De Santis Marco , Tartaglia Silvio , Apicella Massimo , Visconti Daniela , Noia Giuseppe , Valentini Piero , Lanzone Antonio , Santangelo Rosaria , Masini Lucia
Published: June 2024

Background

Toxoplasmosis is a parasitic infection caused by Toxoplasma gondii and is responsible for gestational and congenital infections worldwide. The current standard therapy is based on the administration of Spiramycin to prevent trans‐placental transmission. Other therapies are being studied to reduce the rates of foetal transmission and symptomatic congenital infection.

Objectives

We report our long‐standing experience in maternal toxoplasmosis infection treatment using a combination of Spiramycin–Cotrimoxazole, assessing its effectiveness in preventing vertical transmission compared to the expected incidence of congenital infection.

Methods

We retrospectively collected cases of pregnant women referred to our centre for suspected toxoplasmosis infection according to Lebech criteria, treated with Spiramycin–Cotrimoxazole.

Results

Of 1364 women referred to our centre, postnatal follow‐up of primary toxoplasmosis was available in 562 cases (73.9%). The overall vertical transmission rate was 3.4% in women treated immediately with Spiramycin–Cotrimoxazole after the diagnosis of infection. In comparison, it was 7.7% in women undergoing the same therapy but late or with poor compliance. The foetal transmission rate was 71.4% in untreated cases. All the infected newborns of mother treated adequately with Spiramycin–Cotrimoxazole were asymptomatic afterbirth, while 6/21 infected infants of the inadequate Spiramycin–Cotrimoxazole therapy group had postnatal sequelae (28.5%). The incidence of transmission after appropriate Spiramycin–Cotrimoxazole therapy was significantly lower than the expected rate reported in literature.

Conclusions

A combination of Spiramycin and Cotrimoxazole is safe and effective in preventing foetal congenital toxoplasmosis and reducing sequelae in case of in‐utero infection. The timing and adherence to the therapy are crucial to lowering the risk of congenital infection and neonatal morbidity.
Roughness Investigations on In-Service High-Pressure Compressor Blades—Part II: Roughness Parameterization and Computational Fluid Dynamics-Based Modeling of Its Impact on Turbulent Flows
Authors: Vasilopoulos Ilias , Adami Paolo , Voigt Matthias , Meyer Marcus , Mailach Ronald
Published: June 2024

The two-part publication deals with roughness investigations on in-service high-pressure compressor (HPC) blades, both in terms of measurements and simulations. In this paper (Part II), first, stripe measurements of surface roughness coming from the suction side of the blades are conducted, using a highly accurate Alicona measuring device (see Part I for details of the measurement approach). Then, these roughness distributions are used to construct the walls of zero-pressure-gradient, fully turbulent channel flow simulations. Body-fitted unstructured grids of up to 80 M nodes are generated, on which wall-resolved large eddy simulations (LES) as well as Reynolds-averaged Navier–Stokes (RANS) simulations with the k–ω shear stress transport (SST) turbulence model are performed. The computational fluid dynamics (CFD) setup is first validated on a smooth channel reference case against LES and direct numerical simulations (DNS) data from the relevant literature. In addition, the impact of Reynolds number on several rough channel flow simulations is explored, using two different setups at Reτ = 540 and Reτ = 880. Finally, after an identification of the most important roughness parameters (given the relatively limited database at hand), a new roughness function model is proposed, which would allow the prediction of the flow over a rough surface without the need of geometrically resolving the roughness scales.
Defining the KRAS- and ERK-dependent transcriptome in KRAS-mutant cancers
Authors: Klomp Jeffrey A. , Klomp Jennifer E. , Stalnecker Clint A. , Bryant Kirsten L. , Edwards A. Cole , Drizyte-Miller Kristina , Hibshman Priya S. , Diehl J. Nathaniel , Lee Ye S. , Morales Alexis J. , Taylor Khalilah E. , Peng Sen , Tran Nhan L. , Herring Laura E. , Prevatte Alex W. , Barker Natalie K. , Hover Laura D. , Hallin Jill , Chowdhury Saikat , Coker Oluwadara , Lee Hey Min , Goodwin Craig M. , Gautam Prson , Olson Peter , Christensen James G. , Shen John P. , Kopetz Scott , Graves Lee M. , Lim Kian-Huat , Wang-Gillam Andrea , Wennerberg Krister , Cox Adrienne D. , Der Channing J.
Published: June 2024

How theKRASoncogene drives cancer growth remains poorly understood. Therefore, we established a systemwide portrait of KRAS- and extracellular signal–regulated kinase (ERK)–dependent gene transcription in KRAS-mutant cancer to delineate the molecular mechanisms of growth and of inhibitor resistance. Unexpectedly, our KRAS-dependent gene signature diverges substantially from the frequently cited Hallmark KRAS signaling gene signature, is driven predominantly through the ERK mitogen-activated protein kinase (MAPK) cascade, and accurately reflects KRAS- and ERK-regulated gene transcription in KRAS-mutant cancer patients. Integration with our ERK-regulated phospho- and total proteome highlights ERK deregulation of the anaphase promoting complex/cyclosome (APC/C) and other components of the cell cycle machinery as key processes that drive pancreatic ductal adenocarcinoma (PDAC) growth. Our findings elucidate mechanistically the critical role of ERK in driving KRAS-mutant tumor growth and in resistance to KRAS-ERK MAPK targeted therapies.
The evolution of thermogenesis in mammals
Authors: Grabek Katharine R. , Sprenger Ryan J.
Published: June 2024

Comparative genomics elucidates the steps enabling heat production in fat tissue
In Science Journals
Authors: Smith Keith T. , Maroso Mattia , Osborne Ian S. , Hurtley Stella M. , Szuromi Phil , Jiang Di , Malo Courtney , Ross Sarah H. , Kelly Priscilla N. , Lavine Marc S. , Stern Peter , Ray L. Bryan , Suleymanov Yury , Fogg Christiana , Foley John F.
Published: June 2024

Highlights from the
Science
family of journals
A tool for clarifying expectations in undergraduate research experiences
Authors: Leung Karen , Clement Laurence , Lewis James , Saul Naledi
Published: June 2024

Articulating clear and achievable expectations is fundamental to both education and organizational management. In this article, we provide a simple intervention for clarifying expectations–and establishing that these expectations have been understood–which proved beneficial both to community college interns and to their internship mentors in biotech-related undergraduate research experiences. Internship mentors were asked to utilize a simple Expectation Clarity Tool to outline the expectations, success metrics, baseline assessments, and training strategy and support that would be foundational to their intern’s project. These included expectations around conceptual, technical, performance, and professional skills and behaviors. Concurrently, but independently, community college interns were asked to complete the same type of exercise as a way of identifying gaps in their knowledge and understanding of their mentor’s expectations and their internship project. The mentor’s completed Expectation Clarity Tool was then shared with their intern. As a result of completing this relatively simple intervention, the majority of mentors reported that it increased their confidence as a mentor, taught them a new mentoring skill, changed how they will mentor trainees moving forward, and positively impacted their relationship with their trainee. On the intern side, the majority of interns reported that engaging in this intervention, both as an independent exercise and in obtaining their mentor’s completed Expectation Clarity Tool, increased their confidence as an intern and positively impacted the success of their internship.
In vitro
effects of the new oral β-lactamase inhibitor xeruborbactam in combination with oral β-lactams against clinical
Mycobacterium abscessus
isolates
Authors: Yamatani Izumi , Aono Akio , Fujiwara Keiji , Asami Takahiro , Kamada Keisuke , Morishige Yuta , Igarashi Yuriko , Chikamatsu Kinuyo , Murase Yoshiro , Yamada Hiroyuki , Takaki Akiko , Komiya Kosaku , Mitarai Satoshi
Published: June 2024

Non-tuberculosis mycobacteria (NTM), particularly
Mycobacterium abscessus
subsp.
abscessus
(
M. abscessus
), are increasingly being recognized as etiological agents of NTM pulmonary disease. However, treatment options for
M. abscessus
are limited owing to their natural resistance to most antibiotics, including β-lactams.
M. abscessus
produces a class A β-lactamase, whose activity is inhibited by cyclic boronic acid β-lactamase inhibitors. We aimed to evaluate the
in vitro
effects of xeruborbactam, a cyclic boronic acid β-lactamase inhibitor, against
M. abscessus
when combined with five β-lactams (amoxicillin, tebipenem, cefdinir, cefuroxime, and cefoxitin). The drug susceptibilities of 43
M
.
abscessus
clinical isolates obtained from 43 patients between August 2005 and May 2014 were tested. The MIC results for each β-lactam with or without 4 µg/mL xeruborbactam were examined. Xeruborbactam lowered the MIC
90
values of tebipenem, amoxicillin, cefuroxime, and cefdinir by 5, ≥4, 3, and 3 dilutions, respectively. The MIC
90
values of cefoxitin without xeruborbactam were 32 µg/mL and did not change upon the addition of xeruborbactam. The lowest MIC
90
value was obtained for tebipenem with xeruborbactam. Almost all isolates had an MIC of 4 µg/mL; one isolate had an MIC of 2 µg/mL. With respect to the susceptibility to the same family drug, the number of susceptible isolates increased from 1/43 (2%) to 43/43 (100%) for tebipenem with xeruborbactam. Combining tebipenem and xeruborbactam could be considered an effective all-oral regimen that benefits outpatient treatment of
M. abscessus
pulmonary disease.

IMPORTANCE

Mycobacterium abscessus
subsp.
abscessus
(
M. abscessus
) disease is treated in two phases; injectable drugs for initial followed by others for continuation. There is a need to develop all-oral treatment methods for
M. abscessus
infection, especially in the continuation phase. However, treatment options for
M. abscessus
are limited owing to their natural resistance to most antibiotics. This is the first report to evaluate the in vitro effects of xeruborbactam, a cyclic boronic acid β-lactamase inhibitor capable of inhibiting the class A β-lactamase produced by
M. abscessus
, against 43
M. abscessus
clinical isolates when combined with five β-lactam antibiotics. Xeruborbactam lowered the MIC90 values of tebipenem by five dilutions, and the number of susceptible isolates increased from 1/43 (2%) to 43/43 (100%). We showed that the tebipenem-xeruborbactam combination might be of interest to explore further as a potentially effective oral regimen for outpatient treatment of
M. abscessus
pulmonary disease.
Osteogenesis Imperfecta type 1: like mother, like daughter – Challenges in the perinatal management
Authors: Vasudeva Akhila , Padavagodu Shivananda Roopa , Handigodu Dugappa Arun , Bhat Vivekananda
Published: June 2024

A third gravida with osteogenesis imperfecta (OI) type 1, in her 20s, was referred from the Medical Genetics department at 12+ weeks with a prenatal diagnosis of OI type 1 in this fetus for further management. She was wheelchair-bound and keen to continue this pregnancy. She had medical termination in her two previous pregnancies for OI in the fetuses. Ultrasound at 12+ weeks revealed a short-bent femur with sparing of the long bones of the upper limb. Serial ultrasound revealed progressive affliction of the long bones with falling growth profile and polyhydramnios. She was delivered at 36 weeks by caesarean for breech in labour under regional anaesthesia.

A multidisciplinary approach, patient determination, and good partner support helped in the successful management of this pregnancy.

The neonate had blue sclera, dentigerous imperfecta, bowing of the femur and relatively spared upper limbs. Growth was on the third centile. The mother says she brings the girl for follow-up every 3–6 months to give injection zoledronate. The mother confirms her girl can stand with support, crawl, and speak two-syllable words. Her daughter had to undergo femur corrective osteotomy rush nailing and hip spice application for a closed fracture of the left femur.
Delayed episode of necrotising enterocolitis in an ex-preterm infant after intravitreal administration of low-dose ranibizumab for the treatment of retinopathy of prematurity
Authors: Morotti Francesco , Aversa Salvatore , Barbieri Fabiana , Risso Francesco Maria
Published: June 2024

Retinopathy of prematurity (ROP) and necrotising enterocolitis (NEC) are complications of prematurity. Despite being quite different in terms of incidence, pathogenesis and consequences, both share a pathogenic role of aberrant vascularisation: increased in ROP, deficient for NEC. Current therapy for ROP includes the use of anti-vascular endothelial growth factor (anti-VEGF) agents, which are able to interrupt retinal hypervascularity. Despite being delivered intravitreously, anti-VEGF used in ROP can be absorbed into circulation and exert systemic effects. We present here a case of an ex-27 weeks gestational age infant, presenting multiple NEC risk factors, treated at 2 months of age with low-dose ranibizumab, who developed a large bowel NEC episode in the first week after treatment. We believe that this further report of an association between anti-VEGF agents and NEC could be interesting for the identification of children at risk of severe adverse events and stimulating further research on the topic.
Modified-tension band suturing: ‘the pulling the reins technique’ – a technique for displaced proximal humeral fracture with medial column instability
Authors: Belangero William Dias , de Andrade André Luis Lugnani , Labronici Pedro José , Giordano Vincenzo
Published: June 2024

Fractures of the proximal humerus with medial column instability are challenging and present an unacceptable rate of complications and reoperations. Despite good results reported with the use of locking plates and augmentation techniques using bone graft or a second plate, varus subsidence and fixation failure have been frequently reported. We describe the case of a patient presenting with a complex, multifragmentary proximal humerus fractures successfully treated with open anatomic reduction and internal fixation using a locking plate augmented with lateral traction using three bone anchors in the humerus head. After 18 months, the patient reported fully recovering the mobility and functionality of the operated shoulder. The use of bone anchors pulling the humeral in three different directions like three vectors applied from medial to lateral, posterior to anterior and lateral to anterior help to reduce the most important deformities (varus and retroversion) by applying the tension band principle. This is an interesting approach to avoid primary and secondary reduction loss of the proximal fractures of the humerus with postero-medial cortical defect. The procedure is a good alternative to be used in patients with failure or insufficiency of the medial wall and marked varus.
Prenatal recognition of cerebriform sebaceous naevus
Authors: Lee Yi Jia , Dickinson Jan E
Published: June 2024

Cerebriform sebaceous naevus (CSN) is a rare morphological sebaceous naevus variant and challenging to diagnose prenatally due to its flat, smooth and waxy appearance and lack of association with extracutaneous manifestations.

A multigravida was referred to our tertiary obstetric unit at 24 weeks of gestation for evaluation of fetal auricular lesions. We were able to further characterise the lesions via serial obstetric ultrasound imaging with the aid of three-dimensional (3D) technology. Although the precise diagnosis prenatally was uncertain, the use of 3D technology allowed the reconstruction of the fetal cutaneous lesions for multidisciplinary assessment to facilitate the development of a neonatal management plan. The diagnosis of CSN was made postnatally on biopsy.
Identifying how pre-existing resources combine to shape the experiences of work and family life of a diverse sample of working parents with at least one child in primary school in Scotland during COVID-19 pandemic-related social restrictions: a qualitative descriptive design
Authors: McQueen Fiona , Osborn Sharani
Published: June 2024

Objectives

This study aimed to identify factors that shaped working parents (WPs’) experiences of COVID-19-related social restrictions and analyse the relationships between those factors.

Design

A qualitative descriptive design was used to collect five time points of data including two online questionnaires and three telephone or online interviews between March 2021 and August 2021 with some follow-up interviews in December 2022.

Setting

The COVID-19 pandemic led to social restrictions which greatly impacted WPs who had to both work and look after their children within their home space without any formal childcare.

Participants

19 participants living in Scotland who had at least one child of primary school age and who had been working in March 2020.

Results

All parents were affected by social restrictions during the COVID-19 pandemic, with the flexibility of employers, their socioeconomic situation and the amount of space in their home environment being particularly influential. The impact of social restrictions was greater for lone parents (LPs) due to the inability to share childcare with another adult in the home. Parents in low-income households were affected due to pre-existing inequalities of resources.

Conclusions

These findings indicate several policy options that could mitigate negative outcomes for parents in the case of a future pandemic, including options to lessen inequities experienced by LPs. These include priority access to school places (particularly for children with underlying chronic medical conditions), the ability to establish a ‘support bubble’ at the beginning of social restrictions and being given access to safe outside places for children without a garden.
Strengthening contraceptive counselling services to empower clients and meet their needs: protocol for a two-stage, multiphase complex intervention in Pakistan and Nigeria
Authors: Tran Nguyen Toan , Ali Moazzam , Azmat Syed Khurram , Seuc Armando , Olaolorun Funmilola M , Awan Muhammad Ali , Morhason-Bello Imran , Thom Ellen Mpangananji , Martin Josepth , Abubakar Hanifah Datti , Uzma Qudsia , Kiarie James
Published: June 2024

Background

High-quality contraceptive counselling can accelerate global efforts to reduce the unmet need for and suboptimal use of modern contraceptives. This study aims to identify a package of interventions designed to strengthen in Pakistan and Nigeria and determine their effectiveness in increasing client-level decision-making, autonomy and meeting of contraceptive needs.

Methods

A multisite, two-stage and five-phase intervention design will start with a pre-formative, formative, design, experimental and reflective phase. The pre-formative phase will map potential study sites and establish the sampling frame. The two-part formative phase will first use participatory approaches to identify clients’ perspectives, including young couples and providers, to ensure research contextualisation and address each interest group’s needs and priorities followed by clinical observations of client–provider encounters to document routine care. The design workshop in the third phase will result in the development of a package of contraceptive counselling interventions. In the fourth experimental phase, a multi-intervention, three-arm, single-blinded, parallel cluster randomised-controlled trial will compare routine care (arm 1) with the contraceptive counselling package (arm 2) and the same package combined with wider methods availability (arm 3). The study aims to enrol a total of 7920 participants. The reflective phase aims to identify implementation barriers and enablers. The outcomes are clients’ level of decision-making autonomy and use of modern contraceptives.

Ethics and dissemination

Ethical approval for this study was obtained from the WHO Scientific and Ethics Review Committee (Protocol ID Pakistan: ERC 006232 and Nigeria ERC: 006523). Each study site is required and has obtained the necessary ethical and regulatory approvals that are required in each specific country. Findings will be presented at local, national and international conferences and disseminated by peer-review publications.

Trial registration number

NCT06081842.