bluuebunny/crossref_metadata_2025 huggingface dataset:
Multivalent, BispecificαB7-H3-αCD3 Chemically Self-Assembled Nanorings Direct Potent T-cell Responses Against Medulloblastoma
Authors: Mews Ellie A. , Beckmann Pauline J. , Patchava Mahathi , Wang Yiao , Largaespada David A. , Wagner Carston R.
Published: March 2022

Few therapeutic options have been made available for treating central nervous system tumors, especially upon recurrence. Recurrent medulloblastoma is uniformly lethal with no approved therapies. Recent preclinical studies have shown promising results for eradicating various solid tumors by targeting the overexpressed immune checkpoint molecule, B7-H3. However, due to several therapy-related toxicities and reports of tumor escape, the full potential of targeting this pan-cancer antigen has yet to be realized. Here, we designed and characterized bispecific chemically self-assembling nanorings (CSANs) that target the T cell receptor, CD3ε, and tumor associated antigen, B7-H3, derived from the humanized 8H9 single chain variable fragment (scFv). We show that theαB7-H3-αCD3 CSANs increase T cell infiltration and facilitate selective cytotoxicity of B7-H3+medulloblastoma spheroids and that activity is independent of target cell MHC class I expression. Importantly, non-specific T cell activation against the ONS 2303 medulloblastoma cell line can be reduced by tuning the valency of theαCD3 targeted monomer in the oligomerized CSAN. Intraperitoneal injections ofαB7-H3-αCD3 bispecific CSANs were found to effectively cross the blood-tumor barrier into the brain and elicit significant anti-tumor T cell activity intracranially as well as systemically in an orthotopic medulloblastoma model. Moreover, following treatment withαB7-H3-αCD3 CSANs, intratumoral CD4+and CD8+T cells were found to primarily have a central memory phenotype that displayed significant levels of characteristic activation markers. Collectively, these results demonstrate the ability of our multi-valent, bispecific CSANs to direct potent anti-tumor T cell responses and indicate its potential utility as an alternative or complementary therapy for immune cell targeting of B7-H3+brain tumors.

Significance

This study presentsαB7-H3-αCD3 bispecific CSANs as a promising, new immunotherapeutic option for patients with established B7-H3+medulloblastomas.
Cavitation Induced Fracture of Intact Brain Tissue
Authors: Dougan Carey E. , Song Zhaoqiang , Fu Hongbo , Crosby Alfred J. , Cai Shengqiang , Peyton Shelly R.
Published: March 2022

Nonpenetrating traumatic brain injuries (TBI) are linked to cavitation. The structural organization of the brain makes it particularly susceptible to tears and fractures from these cavitation events, but limitations in existing characterization methods make it difficult to understand the relationship between fracture and cavitation in this tissue. More broadly, fracture energy is an important, yet often overlooked, mechanical property of all soft tissues. We combined needle-induced cavitation (NIC) with hydraulic fracture models to induce and quantify fracture in intact brains at precise locations. We report here the first measurements of the fracture energy of intact brain tissue that range from 1.5 to 8.9 J/m2, depending on the location in the brain and the model applied. We observed that fracture consistently occurs along interfaces between regions of brain tissue. These fractures along interfaces allow cavitation-related damage to propagate several millimeters away from the initial injury site. Quantifying the forces necessary to fracture brain and other soft tissues is critical for understanding how impact and blast waves damage tissue in vivo and has implications for the design of protective gear and tissue engineering.

Significance

Mild injuries associated with concussion and blast waves cause tearing of brain tissue, which leads to traumatic brain injury (TBI). TBI is a leading cause of death and disability among children and young adults in the U.S., with 1.5 million Americans reporting a TBI each year. We introduce a novel approach to visualize these tears in intact brain tissue, and report the energies associated with brain fracture. Quantifying the fracture energy of brain, as we have done here, is critical to understand the forces from injury that lead to TBI.
Automation of plate inoculation and reading reduces process time in the clinical microbiology laboratory, compared to a manual workflow
Authors: Peisach Nicole , Krotkov Natalia , Shaye Rachel , Cárdenas Ana María , Powers Richard L.
Published: March 2022

We evaluated the benefits of automation for clinical microbiology laboratory workflow and compared the time required for culture inoculation and plate reading between manual processes and BD Kiestra (but Kiestra) automation. Kiestra automation consists of different modules, each of which facilitate different tasks and work together from specimen inoculation to results reporting. We tracked the steps and measured the associated times-to-completion for both manual and automated workflows, including number of plate touches, hands-on-time (HOT), total technologist time (TTT), and walk-away time (WAT). Manual and automated processes both included 90 samples, and a total of 180 agar plates. There were three media quantity protocols used to mimic common laboratory samples: 1) 30 ‘urine’ specimens on one biplate; 2) 30 ‘urine’ specimens divided across two plates; and 3) 30 ‘blood’ or ‘wound’ specimens divided across three plates; all cultures incubated for a minimum of 18 hours prior to reading or imaging. Automation reduced HOT by 85% and overall plate touches by 88%. Automated inoculation (through implementation of the BD InoqulA module) resulted in a 100% reduction in plate touches and created 81.5-minutes of WAT. Automation of culture reading (through implementation of the BD ReadA incubation/plate imaging module and BD Synapsys Informatics) reduced HOT by 53%. Overall, laboratory automation resulted in shorter TTT and created WAT when compared to manual processes. Automation can facilitate increased processing capacity, more efficient use of the labor force, and reduced time to results in the clinical microbiology laboratory.
Epidemic Model with Direct and Indirect Transmission modes and Two Delays
Authors: Najm F. , Yafia R. , Alaoui M. A. Aziz , Aghriche A.
Published: March 2022

We propose an epidemic model in which all diseases are transmitted by direct transmission (infectives to susceptibles) and indirect transmission which occurs through shedding of virus by infectives and acquisition by susceptibles. The model takes into account the effect of latency period and time needed for a susceptible to become infective by indirect contact. Under the certain assumptions, the basic reproduction number of the model is identified from the direct and indirect basic reproduction numbers. The main goal is to analyse the asymptotic behaviours, global stability, bifurcation and to detecte the most sensitive parameters. Numerical simulations are carried out to illustrate the theoretical part.
The decay of coronavirus in sewage pipes and the development of a predictive model for the estimation of SARS-CoV-2 infection cases based on wastewater surveillance
Authors: Fu Songzhe , Wang Qingyao , He Fenglan , Zhou Can , Zhang Jin , Xia Wen
Published: March 2022

Wastewater surveillance serves as a promising approach to elucidate the silent transmission of SARS-CoV-2 in a given community by detecting the virus in wastewater treatment facilities. This study monitored the viral RNA abundance at one WWTP and three communities during the COVID-19 outbreak in the Yanta district of Xi’an city from December 2021 to January 2022. To further understand the decay of the coronavirus in sewage pipes, avian infectious bronchitis virus (IBV) was seeded in two recirculating water systems and operated for 90 days. Based on the viral abundance in the wastewater of Xi’an and the above data regarding the decay of coronavirus in sewage pipes, Monte Carol simulations were performed to estimate the infectious cases in Xi’an. The results suggested that the delta variant was first detected on Dec-10, five days earlier than the reported date of clinical samples. SARS-CoV-2 was detected on December 18 in the monitored community two days earlier than the first case and was consecutively detected in the following two sampling times. In pipelines without biofilms, the results showed that high temperature significantly reduced the viral RNA abundance by 2.18 log10 GC/L after experiencing 20 km travel distance, while only a 1.68 log10 GC/L reduction was observed in the pipeline with a low water temperature. After 90 days of operation, the biofilm matured in the pipeline in both systems. Reductions of viral RNA abundance of 2.14 and 4.79 log10 GC/L were observed in low- and high-temperature systems with mature biofilms, respectively. Based on the above results, we adjusted the input parameters for Monte Carol simulation and estimated 23.3, 50.1, 127.3 and 524.2 infected persons in December 14, 18, 22 and 26, respectively, which is largely consistent with the clinical reports. This work highlights the viability of wastewater surveillance for the early warning of COVID-19 at both the community and city levels, which represents a valuable complement to clinical approaches.
[18F]-Labeled PARP-1 PET Imaging of PSMA Targeted Alpha Particle Radiotherapy Response
Authors: Zhang Hanwen , Abou Diane , Villmer Alexandria , Benabdallah Nadia , Jiang Wen , Ulmert David , Carlin Sean , Rogers Buck E. , Turtle Norman F. , McDevitt Michael R. , Baumann Brian , Simons Brian W. , Zhou Dong , Thorek Daniel L. J.
Published: March 2022

Motivation

The growing interest and clinical translation of alpha particle (α) therapies brings with it new challenges to assess target cell engagement and to monitor therapeutic effect. Noninvasive imaging has great potential to guide α-treatment and to harness the potential of these agents in the complex environment of disseminated disease. Poly(ADP) ribose polymerase 1 (PARP-1) is among the most abundantly expressed DNA repair enzymes with key roles in multiple repair pathways - such as those induced by irradiation.

Materials and Methods

Here, we used a third-generation PARP1-specific radiotracer, [18F]-PARPZ, to delineate castrate resistant prostate cancer xenografts. Following treatment with the clinically applied [225Ac]-PSMA-617, positron emission tomography was performed and analyzed, along with and correlative autoradiography and histology acquired.

Results

[18F]-PARPZ was able to distinguish treated from control (saline) xenografts by uptake. Kinetic analysis of tracer accumulation also suggests that the localization of the agent to sites of increased PARP-1 expression is a consequence of DNA damage response.

Conclusions

Together, these data support expanded investigation of [18F]-PARPZ to facilitate clinical translation in the α-therapy space.
A naturally arising broad and potent CD4-binding site antibody with low somatic mutation
Authors: Barnes Christopher O. , Schoofs Till , Gnanapragasam Priyanthi N.P. , Golijanin Jovana , Huey-Tubman Kathryn E. , Gruell Henning , Schommers Philipp , Suh-Toma Nina , Lee Yu Erica , Cetrulo Lorenzi Julio C. , Piechocka-Trocha Alicja , Scheid Johannes F. , West Anthony P. , Walker Bruce D. , Seaman Michael S. , Klein Florian , Nussenzweig Michel C. , Bjorkman Pamela J.
Published: March 2022

The induction of broadly neutralizing antibodies (bNAbs) is a potential strategy for a vaccine against HIV-1. However, most bNAbs exhibit features such as unusually high somatic hypermutation, including insertions and deletions, which make their induction challenging. VRC01-class bNAbs exhibit extraordinary breadth and potency, but also rank among the most highly somatically-mutated bNAbs. Here we describe a VRC01-class antibody isolated from a viremic controller, BG24, that has less than half the mutations of most other relatives of its class, while achieving comparable breadth and potency. A 3.8 Å X-ray crystal structure of a BG24-BG505 Env trimer complex revealed conserved contacts at the gp120 interface characteristic of the VRC01-class Abs, despite lacking common CDR3 sequence motifs. The existence of moderately-mutated CD4-binding site (CD4bs) bNAbs such as BG24 provides a simpler blueprint for CD4bs antibody induction by a vaccine, raising the prospect that such an induction might be feasible with a germline-targeting approach.

Teaser

An anti-HIV-1 antibody with comparable neutralization breadth and potency to similarly-classed antibodies, with half as many mutations.
The Arabidopsis Hop1 homolog ASY1 mediates cross-over assurance and interference
Authors: Pochon Gaetan , Henry Isabelle M , Yang Chao , Lory Niels , Jiménez Nadia Fernández- , Böwer Franziska , Hu Bingyan , Carstens Lena , Tsai Helen T. , Pradillo Monica , Comai Luca , Schnittger Arp
Published: March 2022

The chromosome axis plays a crucial role in meiotic recombination. Here, we study the function of ASY1, the Arabidopsis homolog of the yeast chromosome axis associated component Hop1. Specifically, we characterized cross-over (CO) distribution in female and male meiosis by deep sequencing of the progeny of an allelic series ofasy1mutants. Combining data from nearly 1000 individual plants, we find that reduced ASY1 activity leads to genomic instability and sometimes drastic genomic rearrangements. We further observed that COs are less frequent and appear in more distal chromosomal regions in plants with no or reduced ASY1 activity, consistent with previous analyses. However, our sequencing approach revealed that the reduction in CO number is not as dramatic as suggested by cytological analyses. Analysis of double mutants ofasy1with mutants with three other CO factors, MUS81, MSH4 and MSH5 as well as the determination of foci number of the CO regulator MLH1 demonstrates that the majority of the COs inasy1, similar to the situation in the wildtype, largely belong to the class I, which are subject to interference. However, these COs are redistributed inasy1mutants and typically appear much closer than in the wildtype. Hence, ASY1 plays a key role in CO interference that spaces COs along a chromosome. Conversely, since a large proportion of chromosomes do not receive any CO, we conclude that CO assurance, the process that ensures the obligatory assignment of one CO per chromosome, is also affected inasy1mutants.

Significant statement

The regulation of the number and placement of cross-overs (COs) during meiosis is critical to ensure meiotic fidelity and promote new genetic combinations. Here, we investigated the function of one of the proteins of the chromosome axis, which plays a key role in CO formation: ASY1. Our results show that COs inasy1mutants are positioned closer to each other than in the wildtype and that, despite a roughly similar number of COs, not every chromosome receives a CO. With this, our results shed light on the mechanisms regulating two important but still poorly understood aspects of meiosis: CO assurance, which safeguards at least one CO per chromosome pair, and CO interference, which prevents two COs from occurring close to each other.
Proteome reallocation enables the selective de novo biosynthesis of non-linear, branched-chain acetate esters
Authors: Seo Hyeongmin , Giannone Richard J. , Yang Yung-Hun , Trinh Cong T.
Published: March 2022

The one-carbon recursive ketoacid elongation pathway is responsible for making various branched-chain amino acids, aldehydes, alcohols, and acetate esters in living cells. Controlling selective microbial biosynthesis of these target molecules at high efficiency is challenging due to enzyme promiscuity, regulation, and metabolic burden. In this study, we present a systematic modular design approach to control proteome reallocation for selective microbial biosynthesis of branched-chain acetate esters. Through pathway modularization, we partitioned the branched-chain ester pathways into four submodules including keto-isovalerate submodule for converting pyruvate to keto-isovalerate, ketoacid elongation submodule for producing longer carbon-chain keto-acids, ketoacid decarboxylase submodule for converting ketoacids to alcohols, and alcohol acyltransferase submodule for producing branched-chain acetate esters by condensing alcohols and acetyl-CoA. By systematic manipulation of pathway gene replication and transcription, enzyme specificity of the first committed steps of these submodules, and downstream competing pathways, we demonstrated selective microbial production of isoamyl acetate over isobutyl acetate. We found that the optimized isoamyl acetate pathway globally redistributed the amino acid fractions in the proteomes and required up to 23-31% proteome reallocation at the expense of other cellular resources, such as those required to generate precursor metabolites and energy for growth and amino acid biosynthesis. The engineered strains produced isoamyl acetate at a titer of 8.8 g/L (> 0.25 g/L toxicity limit), a yield of 0.17 g/g (47% of maximal theoretical value), and 86% selectivity, achieving the highest titers, yields and selectivity of isoamyl acetate reported to date.
Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains
Authors: Case James Brett , Mackin Samantha , Errico John , Chong Zhenlu , Madden Emily A. , Guarino Barbara , Schmid Michael A. , Rosenthal Kim , Ren Kuishu , Jung Ana , Droit Lindsay , Handley Scott A. , Halfmann Peter J. , Kawaoka Yoshihiro , Crowe James E. , Fremont Daved H. , Virgin Herbert W. , Loo Yueh-Ming , Esser Mark T. , Purcell Lisa A. , Corti Davide , Diamond Michael S.
Published: March 2022

Omicron variant strains encode large numbers of changes in the spike protein compared to historical SARS-CoV-2 isolates. Although in vitro studies have suggested that several monoclonal antibody therapies lose neutralizing activity against Omicron variants1-4, the effects in vivo remain largely unknown. Here, we report on the protective efficacy against three SARS-CoV-2 Omicron lineage strains (BA.1, BA.1.1, and BA.2) of two monoclonal antibody therapeutics (S309 [Vir Biotechnology] monotherapy and AZD7442 [AstraZeneca] combination), which correspond to ones used to treat or prevent SARS-CoV-2 infections in humans. Despite losses in neutralization potency in cell culture, S309 or AZD7442 treatments reduced BA.1, BA.1.1, and BA.2 lung infection in susceptible mice that express human ACE2 (K18-hACE2). Correlation analyses between in vitro neutralizing activity and reductions in viral burden in K18-hACE2 or human Fcγ R transgenic mice suggest that S309 and AZD7442 have different mechanisms of protection against Omicron variants, with S309 utilizing Fc effector function interactions and AZD7442 acting principally by direct neutralization. Our data in mice demonstrate the resilience of S309 and AZD7442 mAbs against emerging SARS-CoV-2 variant strains and provide insight into the relationship between loss of antibody neutralization potency and retained protection in vivo.
The role of social entrepreneurial leadership and benchmarking in women empowerment
Authors: Dixit Abha R. , Malik Nishtha , Seth Manisha , Sethi Deepa
Published: March 2022

Purpose

Women are the change agents in today's society. They are not only the harbingers of growth and development but also act as a major catalyst in the economic advancement and prosperity of the nation. India has been witnessing an expansion in women entrepreneurs given the conducive startup ecosystem we have created over the years. It has inspired women to break the shackles and switch to being a game changer for themselves and many others over the years. The study aims to explore the impact of social entrepreneurial leadership on women empowerment and how does benchmarking help in this process.

Design/methodology/approach

Using a semi-structured questionnaire, the study conducted one-to-one in-depth and focused group interviews with the five women social entrepreneurs and their team. NVivo was used for content and thematic analysis.

Findings

Major themes identified from the study include financial independence, women empowerment, social identity, autonomy, mobility, attaining self-confidence, creativity and innovation, fulfillment of motives, action and social learning, and setting standards (benchmarks). The findings revealed that social entrepreneurial leadership has a significant impact on women empowerment through benchmarking.

Originality/value

Social entrepreneurial leadership has the potential to revolutionize the very concept of women empowerment. The research tries to study specific cases of social entrepreneurial leadership and how they have been instrumental in shaping up the life of others through their efforts and determination.
Understanding the effectiveness of gamification in an industrial work process: an experimental approach
Authors: Jacob Axel , Faatz Andreas , Knüppe Lars , Teuteberg Frank
Published: March 2022

Purpose

In this paper, the authors report the findings of an experiment on the effectiveness of gamification on work performance in a real industrial workplace setting with monotonous, repetitive work.

Design/methodology/approach

The authors conducted an experiment with a simple gamification application that the authors added to a given information system and compared the work performance of an experimental group (n = 16) with a control group (n = 15) over a period of one month.

Findings

The results of the authors’ experiment show that gamification of the workplace leads to a measurable improvement of work performance, creates prevailingly positive emotions and increases the motivation of the workers.

Research limitations/implications

The authors’ findings provide reasons for conducting future research on the contiguity of gamification and the Hawthorne effect or similar phenomena. In this regard, it also seems necessary to take a closer look at who is really affected by a gamified environment and what the boundaries of the gamified environment are.

Practical implications

The authors demonstrate that gamification is a useful tool for process improvement. Furthermore, our results are helpful for a more successful implementation of gamification.

Originality/value

Gamification has proven to be effective in a large number of application contexts, such as education, health and crowdsourcing. Despite the generally positive evaluation of its effectiveness, gamification is still thought to work differently in different contexts. Therefore, there is a gap in the literature on this topic with respect to real industrial workplaces. To the best of the authors’ knowledge, the authors are among the first to have conducted a gamification experiment in a real industrial context.
The impact of age-specific minimum wages on youth employment and education: a regression discontinuity analysis
Authors: Dayioglu Meltem , Küçükbayrak Müşerref , Tumen Semih
Published: March 2022

Purpose

Using a regression discontinuity design in tandem with a difference-in-discontinuities analysis, the study finds that increasing the minimum wage reduces the employment probability of young males by 2.5–3.1 percentage points.

Design/methodology/approach

The authors exploit an age-specific minimum wage rule – which sets a lower minimum wage for workers of age 15 than the adult minimum wage paid to workers of age 16 and above – and its abolition to estimate the causal effect of a minimum wage increase on youth employment and education in Turkey.

Findings

The authors also document that, initially, the minimum wage increase does not lead to a major change in high school enrollment, while the likelihood of transitioning into “neither in employment nor in education and training” (NEET) category notably increases. However, in the medium term, the NEET effect is transitory; school enrollment increases over time and absorbs the negative employment effect.

Originality/value

The authors argue that policy effects have mostly been driven by demand-side forces rather than the supply side.
Performance measurement and management system 4.0: an action research study in investee NPOs by local government
Authors: Sardi Alberto , Sorano Enrico , Giovando Guido , Tradori Vania
Published: March 2022

Purpose

The Fourth Industrial Revolution is increasing the use of digital technologies for delivering products and services. A performance measurement and management system (PMMS) is recognised as a useful system to guide era 4.0; however, the literature has not adequately addressed this challenge in public government and not-for-profit organisations (NPOs). This research aims to investigate the evolution of the PMMS adopted by a local government for the control of investee NPOs in era 4.0.

Design/methodology/approach

Through action research, the authors investigate an Italian municipality and its main investee NPOs. The project involved 4 researchers and 25 managers of the local government and NPOs.

Findings

This paper describes the design of a PMMS developed for a local government to control its investee NPOs. Considering the regulations and managerial needs, the designed system evolved from a fragmented set of indicators based on legitimacy and economic perspectives to a holistic set of indicators based on a comprehensive set of perspectives to consider the changing business environment.

Originality/value

This study sheds light on the design of a PMMS adopted by local governments for controlling investee NPOs in era 4.0. The paper contributes (1) to identify the main control needs for the design of a PMMS in a public network and (2) to capture the evolution of a PMMS in light of era 4.0 by developing two conceptual propositions.
Examining the effect of self-regulation failure on academic achievement in emergency remote teaching and learning versus face-to-face
Authors: Boshoff-Knoetze Anet , Duminy Lize , Du Toit Yadah
Published: March 2022

Purpose

The study aimed to examine the relationship between self-regulation failure and academic achievement in an emergency remote teaching (ERT) and learning environment compared to a face-to-face setting.

Design/methodology/approach

This study conducted an analysis of covariance (ANCOVA) to investigate the impact of students falling behind (as proxy for self-regulation failure) on their final course mark. The sample comprised students from four undergraduate modules offered at a South African university in a face-to-face setting (N = 1,604), as well as an ERT setting (N = 1,478). Students falling behind were measured as the days behind, relative to the academic program, using learning management system (LMS) log data. The study further explored whether self-regulation failure had a greater effect on academic achievement in ERT as opposed to a face-to-face context.

Findings

The results indicated a negative correlation between self-regulation failure, evidenced by falling further behind in the academic program, and students' final course marks. Furthermore, the negative impact of falling behind was found to be greater on a student's final course mark during ERT compared to a face-to-face setting.

Originality/value

This study contributes to the literature on ERT by highlighting the increased negative effect of self-regulation failure on academic achievement in ERT as opposed to face-to-face teaching and learning. Findings of this research may be of value to educators and policymakers in identifying ways of supporting self-regulated learning in future ERT situations to ensure that academic success is maintained.
The international transfer of individual career capital: exploring and developing a model of the underlying factors
Authors: Oleškevičiūtė Emilija , Dickmann Michael , Andresen Maike , Parry Emma
Published: March 2022

Purpose

The purpose of this literature review is to critically analyze, synthesize and integrate the currently fragmented literature concerning the factors affecting the international transfer of individual career capital (CC).

Design/methodology/approach

This paper is a systematic literature review of the factors affecting the international transfer of individual CC from/for expatriates, repatriates and other employed highly skilled migrants and return migrants. The findings are classified based on the Social Chronology Framework (SCF) proposed by Gunz and Mayrhofer (2015).

Findings

This systematic literature review suggests that the international transfer of individual CC, which can be expressed both as (1) individual-level transfer across different organizations located in different countries as the direct use and application of CC and (2) individual knowing-how transfer to other individuals within organization, is affected by the individual, organizational and broader contextual-level factors that are bound by the aspect of time. The authors summarize the findings by presenting a model of the factors affecting the international transfer of individual CC.

Originality/value

The authors align the CC framework (Defillippi and Arthur, 1994) to the SCF (Gunz and Mayrhofer, 2018) by explaining the factors affecting the international transfer of individual CC that go beyond the qualities of CC, including the Being, Space and Time domains. Moreover, the authors critique the current focus on the international CC transfer in the present suggesting that future research should explore this phenomenon as a more dynamic process. Finally, the authors contribute to the literature on the global mobility of highly skilled employees' by highlighting gaps in the knowledge of the international transfer of CC and presenting a future research agenda.
“One of the team” patient experience of integrated breast cancer care
Authors: Tucker Helen
Published: March 2022

Purpose

This paper presents my experience of breast cancer care in which I describe my care as positive and integrated.

Design/methodology/approach

I have applied an autoethnographical approach to my patient story to analyse my care in order to reflect and share insights. I have applied my knowledge and experience in integrated care through my research, management and practice.

Findings

In my patient story I describe being empowered and feeling like “one of the team.” Vertical and horizontal integration was evident across staff services and agencies. This included integrated working across multi‐disciplinary teams, between primary and secondary care and also between the NHS and a voluntary agency. I identified features that were important to me in my care under the headings of: certainty, communication, contact, compassion, continuity, cohesive, care and collaboration.

Practical implications

I consider the implications of sharing patient stories to inform quality improvement, influence education and training for staff and design support for patients. I consider how patients can be more involved in the evaluation of their care.

Originality/value

This viewpoint has been written from my perspective as a patient and a professional, and was written in order to recognise good practice and share the learning for continual quality improvement. There is every sign that person-centred integrated care is starting to be embedded in some of our services and hopefully this will be recognised, celebrated and sustained.
Why are ‘suboptimal’ temperatures preferred in a tropical intertidal ectotherm?
Authors: Hui T. Y. , Crickenberger Sam , Lau Jackson W. T. , Williams Gray A.
Published: March 2022

In thermally extreme environments, it is challenging for organisms to maximize performance due to risks associated with stochastic variation in temperature and, subsequently, over evolutionary time minimizing the exposure to risk can serve as one of the mechanisms that result in organisms preferring suboptimal temperatures.

We tested this hypothesis in a slow‐moving intertidal snail on tropical rocky shores, where temperature variability increases with time from 30 min to 20 hr when recorded at 30 min intervals (due to short‐term environmental autocorrelation where temperatures closer in time are more similar as compared to temperatures over a long period of time). Failure to accommodate temporal variation in thermal stress by selecting cool habitats can result in mortality.

Thermal performance curves for different traits (heart rate and locomotion) were measured and compared to the snail's thermal preferences in both the field and laboratory. Predicted performances of the snails were simulated based on thermal performance curves for different traits over multiple time‐scales and simulated carryover effects.

A strong mismatch was found between physiological and behavioural thermal maxima of the snails (physiological thermal maximum being higher by ~7°C), but the snails avoided these maxima and sought temperatures 7–14°C cooler. Such a risk‐averse strategy can be explained by their predicted performances where the snails should make decisions about preferred temperatures based on time periods ≥5 hr to avoid underestimating the temporal variation in body temperature.

In extreme and stochastic environments, where the temporal variation in environmental conditions can lead to substantial divergence between instantaneous and time‐averaged thermal performances, ‘cooler is better’ and ‘suboptimal’ body temperatures are preferred as they provide sufficient buffer to reduce mortality risk from heat stress.
Edible zombis: fresh fish and the industry of cosmetic corpses
Authors: Baptista João Afonso , Truninger Monica
Published: March 2022

Doing research on fishery commodities in Portugal led us to an enigma: for a dead fish to befresco(fresh) it must be alive. This paradox manifests at a popular, commercial, and legal level. It denotes the interruption of the difference between being dead and being alive in the commodity form. In Portugal, we suggest, the commercialization ofpeixefresco(fresh fish) is based on the production and consumption of edible ‘zombis’: seafood corpses technologically and symbolically crafted as undead. An open concept, ‘edible zombis’ is part of an experimental vocabulary that foregrounds the productive agency of undeadness, both biological and commercial, in the seafood economic complex. It relates to the ordinary practice of necromancy in the commodity‐based world. Edible zombis are commodity fetishes that fetishize their producers and consumers, suspending them from the capitalist system in which they live.
Larvicidal activity of leaf extract of Nerium oleander L. and its synthesized metallic nanomaterials on dengue vector, Aedes aegypti
Authors: Al‐Hakimi Ahmed N. , Abdulghani Mahfoudh A.M. , Alhag Sadeq K. , Aroua Lotfi M. , Mahyoub Jazem A.
Published: March 2022

The development of natural insecticide from plant products may have a beneficial effect as a promising candidate for practical strategies for controlling vector‐borne diseases without current treatment. The present study was carried out to characterize green synthesized metallic nanomaterials for silver (Ag‐NPs) and gold (Au‐NPs) from extract leaf of Nerium oleander L., assess in vivo toxicity, and evaluate the larvicidal activity against Aedes aegypti. The prepared nanomaterials (Ag‐NPs and Au‐NPs) were characterized by Ultraviolet–Visible Spectroscopy (UV–Vis), Fourier transform infrared spectroscopy (FTIR), X‐ray diffraction (XRD), and transmission electron microscopy (TEM). In addition, the subacute in vivo toxicity method was used to assess the extract and the nanomaterials (Ag‐NPs and Au‐NPs); in evaluating larvicidal activities using the World Health Organization (WHO) method. The Ag‐NPs and Au‐NPs were confirmed by shifting the absorption band in UV–Vis, FTIR spectrums toward higher wavelengths. TEM and XRD analysis were revealed that the average particle size of Au‐NPs and Ag‐NPs showed 15.30 and 11.48 nm, respectively. In the toxicity experiment, no mortality or signs of toxicity were reported in all groups of treated animals; in larvicidal activity, the Au‐NPs and Ag‐NPs with LC50 36.0716 and 46.645 ppm respectively showed more effectiveness than leaf extract alone 108.1665 ppm. Collectively, extract leaf of N. oleander L. can be efficiently used to synthesize metallic nanomaterials with silver and gold, which can be adopted as a natural source of insecticide against Ae. aegypti.
Neuroendocrine tumor secondary to pulmonary hypoplasia: A case report
Authors: Yukawa Takuro , Ishida Yuta , Naomoto Yoshio , Monobe Yasumasa , Fukazawa Takuya , Yamatsuji Tomoki
Published: March 2022

Pulmonary hypoplasia is diagnosed during the perinatal period and is a cause of death in newborns. However, these developmental abnormalities are diagnosed in adulthood in some cases. A 70‐year‐old male smoker was diagnosed with stage IIIA pulmonary adenocarcinoma in the right upper lobe with right middle lobe hypoplasia. He subsequently underwent right upper and middle lobectomy with lymph node dissection by video‐assisted thoracoscopic surgery. In addition to an invasive adenocarcinoma in the right upper lobe, pathological examination of the hypoplastic lobe revealed neuroendocrine hyperplasia, as well as tumorlets and a typical carcinoid. Eight cases of pulmonary neuroendocrine tumors that developed from pulmonary hypoplasia have been reported to date. Interestingly, all but one case occurred in the right middle lobe. Neuroendocrine cell hyperplasia has been reported to develop in hypoplastic lungs postnatally; therefore, we speculated that the lesion was the origin of these neuroendocrine tumors. Moreover, the pathological findings suggested that atelectasis was involved in the pathogenesis of this rare condition. In adults, when lobar hypoplasia is diagnosed, neuroendocrine tumors should be anticipated.
Subsidized Common Agricultural Policy grazing jeopardizes the protection of biodiversity and Natura 2000 targeted species
Authors: Kindvall O. , Franzén M. , Askling J. , Forsman A. , Johansson V.
Published: March 2022

In Europe, Natura 2000 sites should protect threatened target species and networks of habitats. The management of Natura 2000 grasslands is often financed by subsidized grazing as part of the Common Agricultural Policy (CAP). We studied the extent of CAP grazing for Natura 2000 management and how this affects a butterfly target species (the marsh fritillary) and floral resources. Based on extensive capture‐mark‐release studies from 2 years in >550 ha grid cells in a 225 km2landscape in Sweden that includes 15 Natura 2000 sites, we compared marsh fritillary occurrence probabilities and population densities in ungrazed and CAP‐grazed habitats. Moreover, we analyzed how nectar resources and orchids were affected by CAP grazing based on plants records from 2347 sample plots. We estimated the proportion of butterfly habitats that were CAP‐grazed within and outside Natura 2000 sites. In total, 10 453 and 4417 butterflies were marked in 2017 and 2019, respectively. The grid cell occurrence probability was 1.8 times higher and the population density was 2.3 times higher in ungrazed compared with CAP‐grazed habitats in 2017, and the corresponding numbers for 2019 were 10 and 5.3 times higher, respectively. The number of flowering plants were on average 6.9 times higher and the density of orchids was 12.3 times higher in ungrazed habitats. Roughly, 30% (130 ha) of the marsh fritillary habitat was CAP grazed, and 97% of this grazing occurred within protected areas, of which 111 ha was situated within Natura 2000 area where the marsh fritillary is the target species. Alarmingly, we show that intense yearly CAP grazing, which is the dominant management strategy in all Natura 2000 sites, has devastating consequences for the target species and other aspects of biodiversity. Less intense management, which would benefit biodiversity, requires changes in the CAP, to allow more flexible payments for habitat management objectives and conservation of target species.
Sortition as Anti‐Corruption: Popular Oversight against Elite Capture
Authors: Bagg Samuel
Published: March 2022

Random selection for political office—or “sortition”—is increasingly seen as a promising tool for democratic renewal. Critics worry, however, that replacing elected and appointed officials with randomly selected citizens would only exacerbate elite manipulation of political processes. This article argues that sortitioncancontribute to democratic renewal, but that its genuine promise is obscured by the excessive ambition and misplaced focus of prevailing models. Casting random selection as a route to accurate representation of the popular will, most contemporary proposals require randomly selected citizens to perform legislative tasks, whose open‐endedness grants substantial discretion to elite agenda setters and facilitators. The real democratic promise of sortition‐based reforms, I argue, lies in obstructing elite capture at critical junctures: a narrower task of oversight that creates fewer opportunities for elite manipulation. In such contexts, the benefits of empowering ordinary people—resulting from their immunity to certain distorting influences on career officials—plausibly outweigh the risks.
Intrinsic religiosity and counterproductive work behavior: The mediating role of Islamic work ethic
Authors: Gürlek Mert
Published: March 2022

This research aims to examine the impact of intrinsic religiosity on counterproductive work behavior directed toward the organization (CWB‐O) and the mediating role of Islamic work ethic in this impact. The data were collected from employees working in the hotel and restaurant industry (n = 684). The findings revealed that intrinsic religiosity had a positive and significant effect on Islamic work ethic. It was found that Islamic work ethic also had a negative and significant effect on CWB‐O. Similarly, intrinsic religiosity had a negative and significant effect on CWB‐O. In addition, it was identified that the Islamic work ethic had a mediating role in the impact of intrinsic religiosity on CWB‐O. Taking into consideration that the relationship between intrinsic religiosity and CWB‐O and the role of Islamic work ethic in this relationship has not yet been examined in literature, the theoretical contribution of the current research can be better understood. From the perspective of practical contribution, this research may help and guide managers to understand how intrinsic religiosity affects CWB‐O.
Between the Museum and the Street: Roberto Matta's Works in Chile during the Unidad Popular
Authors: Caro Troncoso Paulina
Published: March 2022

This article seeks to contribute to the study of the work Roberto Matta made in Chile in the early 1970s by focusing on a series of painted arpilleras made at Museo Nacional de Bellas Artes and El primer gol del pueblo chileno, a mural created in collaboration with the muralist group Brigada Ramona Parra. I argue that this body of work was largely informed by the ideals of the Unidad Popular and that the artist's presence in the country might have contributed to the institutional validation of popular practices such as crafts and muralism in the local artistic scene.
Host‐directed anti‐mycobacterial activity of colchicine, an anti‐gout drug, via strengthened host innate resistance reinforced by the IL‐1β/PGE2 axis
Authors: Kwon Kee Woong , Kim Lee‐Han , Kang Soon Myung , Lee Ju Mi , Choi Eunsol , Park Jiyun , Hong Jung Joo , Shin Sung Jae
Published: March 2022

Background and Purpose

To diversify and expand possible tuberculosis (TB) drug candidates and maximize limited global resources, we investigated the effect of colchicine, an FDA‐approved anti‐gout drug, against Mycobacterium tuberculosis (Mtb) infection because of its immune‐modulating effects.

Experimental Approach

We evaluated the intracellular anti‐Mtb activity of different concentrations of colchicine in murine bone marrow‐derived macrophages (BMDMs). To elucidate the underlying mechanism, RNA sequencing, biological and chemical inhibition assays, and Western blot, quantitative real‐time PCR, enzyme‐linked immunosorbent assay (ELISA), and immunohistochemical analyses were employed. Finally, type I interferon‐dependent highly TB‐susceptible A/J mice were challenged with virulent Mtb H37Rv, and the host‐directed therapeutic effect of oral colchicine administration on bacterial burdens and lung inflammation was assessed 30 days post‐infection (2.5 mg·kg−1 every 2 days).

Key Results

Colchicine reinforced the anti‐Mtb activity of BMDMs without affecting cell viability, indicating that colchicine facilitated macrophage immune activation upon Mtb infection. The results from RNA sequencing, NLRP3 knockout BMDM, IL‐1 receptor blockade, and immunohistochemistry analyses revealed that this unexpected intracellular anti‐Mtb activity of colchicine was mediated through NLRP3‐dependent IL‐1β signalling and Cox‐2‐regulated PGE2 production in macrophages. Consequently, the TB‐susceptible A/J mouse model showed remarkable protection, with decreased bacterial loads in both the lungs and spleens of oral colchicine‐treated mice, with significantly elevated Cox‐2 expression at infection sites.

Conclusions and Implications

The repurposing of colchicine against Mtb infection in this study highlights its unique function in macrophages upon Mtb infection and its novel potential use in treating TB as host‐directed or adjunctive therapy.
Does early childhood education help to improve high school outcomes? Results from Tulsa
Authors: Amadon Sara , Gormley William T. , Claessens Amy , Magnuson Katherine , Hummel‐Price Douglas , Romm Katelyn
Published: March 2022

Early childhood education contributes to improved school readiness but impacts on high school remain unclear. This study estimates the effects of Tulsa, Oklahoma's universal pre‐K and Head Start programs through the junior year of high school (in 2018/2019; N = 2902; Mage = 16.52, SD = .39; 48% female; 28% white, 34% Black, 27% Hispanic, 8% Native American). Propensity score weighted regressions suggest students who attended pre‐K, but not Head Start, missed less school, were less likely to fail courses and be retained in grade, were more likely to take an Advanced Placement/International Baccalaureate course, but did not have higher test scores or grades. Subgroup analyses by race/ethnicity demonstrated some differences in the pattern of associations favoring students of color.
Efficacy of N‐acetyl aspartyl glutamic acid versus fluorometholone for treating allergic conjunctivitis in an environmental exposure chamber
Authors: de Blay Frédéric , Gherasim Alina , Domis Nathalie , Choual Ibrahim , Bourcier Tristan
Published: March 2022

Background

Topical mast cell stabilizers were previously shown to treat the signs and symptoms of seasonal and perennial allergic conjunctivitis safely and effectively in active and placebo‐controlled trials. However, mast cell stabilizers have not been compared to topical corticosteroids for efficacy. We tested the non‐inferiority of a topical mast cell stabilizer, N‐acetyl aspartyl glutamic acid (4.9%, NAAGA), compared to fluorometholone (0.1%, FM) during controlled exposures to the airborne birch pollen allergen, Bet v 1, in an environmental exposure chamber (EEC).

Methods

This randomized, cross‐over, investigator‐blinded study included 24 patients with a history of birch pollen allergic conjunctivitis. Patients were randomized to 5 days of treatment with NAAGA, then FM (n = 12) or FM, then NAAGA (n = 12). After each treatment, patients were exposed to a fixed airborne concentration of Bet v 1 in ALYATEC EEC. The primary endpoint was the amount of allergen required to trigger a conjunctival response (Abelson score ≥5). Groups were compared with a linear model for cross‐over studies. Non‐inferiority was assumed, when the lower bound of the risk ratio confidence interval (CI) was >0.5.

Results

At screening, the mean time‐to‐conjunctival response was 72.5 ± 35.9 min. NAAGA and FM extended the response time to 114.8 ± 55.0 and 116.6 ± 51.5 min respectively. The mean amounts of allergen required to trigger a conjunctival response were 1.165 ng after NAAGA and 1.193 ng after FM treatment. The risk ratio for the conjunctival response was 0.977 (95% CI: 0.812; 1.174), which indicated non‐inferiority. Adverse events occurred less frequently with NAAGA (29.2%) than with FM (58.3%).

Conclusion

In patients with allergic conjunctivitis to birch pollen, NAAGA was non‐inferior to FM in exposures to airborne Bet v 1. The EEC was a good model for simulating real‐life airborne allergen exposure and for demonstrating the efficacy and safety of eye drops for treating allergic conjunctivitis.

Trial registration

Not registered.