bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutrophil-vascular interactions drive myeloperoxidase accumulation in the brain in Alzheimer’s disease
Authors: Smyth Leon C. D. , Murray Helen C. , Hill Madison , van Leeuwen Eve , Highet Blake , Magon Nicholas J. , Osanlouy Mahyar , Mathiesen Sophie N. , Mockett Bruce , Singh-Bains Malvindar K. , Morris Vanessa K. , Clarkson Andrew N. , Curtis Maurice A. , Abraham Wickliffe C. , Hughes Stephanie M. , Faull Richard L. M. , Kettle Anthony J. , Dragunow Mike , Hampton Mark B.
Published: March 2022

Introduction

Neutrophil accumulation is a well-established feature of Alzheimer’s disease (AD) and has been linked to cognitive impairment by modulating disease-relevant neuroinflammatory and vascular pathways. Neutrophils express high levels of the oxidant-generating enzyme myeloperoxidase (MPO), however there has been controversy regarding the cellular source and localisation of MPO in the AD brain.

Materials and methods

We used immunostaining and immunoassays to quantify the accumulation of neutrophils in human AD tissue microarrays and in the brains of APP/PS1 mice. We also used multiplexed immunolabelling to define the presence of NETs in AD.

Results

There was an increase in neutrophils in AD brains as well as in the murine APP/PS1 model of AD. Indeed, MPO expression was almost exclusively confined to S100A8-positive neutrophils in both human AD and murine APP/PS1 brains. The vascular localisation of neutrophils in both human AD and mouse models of AD was striking and driven by enhanced neutrophil adhesion to small vessels. We also observed rare infiltrating neutrophils and deposits of MPO around plaques. Citrullinated histone H3, a marker of neutrophil extracellular traps (NETs), was also detected in human AD cases at these sites, indicating the presence of extracellular MPO in the vasculature. Finally, there was a reduction in the endothelial glycocalyx in AD that may be responsible for non-productive neutrophil adhesion to the vasculature.

Conclusion

Our report indicates that vascular changes may drive neutrophil adhesion and NETosis, and that neutrophil-derived MPO may lead to vascular oxidative stress and be a relevant therapeutic target in AD.
Metallurgical and corrosion characterization of warring states period bronzes excavated from Pujiang, Chengdu, China
Authors: Liu Liu , Zhong Qing , Jiang Luman , Li Pei , Xiao Lin , Gong Yangmin , Zhu Zhanyun , Yang Junchang
Published: March 2022

Located in Pujiang, Chengdu, China, more than four hundred artifacts were unearthed during the excavation of the Warring States (the Warring States period lasts from 475 to 221 BC) ship-shaped graves in 2016. The compositional and metallurgical feature of the unearthed vessels are still unclear. Archaeologists and conservators are puzzled by such problems that need to be answered by systematic scientific studies. Fifty one samples, either from the matrix (26 samples), or from the corrosion part (25 samples) of 25 unearthed bronze vessels, were carefully collected from the fallen part of the bronze vessels for analysis. Technical methods, such as OM, SEM-EDS, XRD and Raman Spectroscopy were adopted for compositional and metallurgical characterization of the bronzes, as well as identification of the corrosion products. The bronzes are Cu–Sn–Pb trinary alloys with typical casting microstructure. The proportion of Sn are in accordance with excavated bronze vessels in surrounding areas. Recycling isn’t involved with the production of such vessels. Layered structure of the corrosion products was observed. Different corrosion products were identified as Cu2CO3(OH)2, Cu2O, CuSO4·5H2O SnO2, PbSO4 and PbCO3. The findings help us gain insights into the bronze manufacturing in Bashu district, as well as the corrosion behavior in certain condition.
The impact of grandchild care provision on grandparents’ depressive symptoms across Europe using multi-level analysis: do the grandchild caring patterns and the country’s economy matter?
Authors: Yang Yazhen , Evandrou Maria , Vlachantoni Athina
Published: March 2022

Little research has examined the cross-national differences in the impact of grandchild care provision on the grandparents’ depression, by taking into account of both macro- and micro-level factors. This study used a unique grandchild caring pattern variable in order to examine the effect of the changes in the intensity of grandchild caring on the grandparents’ depressive symptoms in European countries, and whether the grandparents’ country level economy influenced such effect. Longitudinal data derived from the Survey of Health, Ageing, and Retirement in Europe 2010–2018 covered 13 countries and 24,656 grandparents aged 50–90. Multi-level linear regression analyses with REML estimation were used. This study found that providing grandchild care had a protective effect against grandparents’ depressive symptoms in both lower and higher income countries. Moreover, providing more intensive grandchild care reduced the grandparents’ depressive symptoms to a greater extent in lower income countries than higher income countries. In addition, grandmothers benefited more from grandchild caring than grandfathers, and the gender gap in the effects of grandchild care provision on one’s depressive symptoms was wider in lower income countries than higher income countries in Europe. Future research can further investigate the mechanisms behind such results. The research findings can be used to develop targeted interventions aimed at grandparents providing childcare of different intensity.
Prevalence and risk factors associated with SARS-CoV-2 infections among veterinary practitioners and dogs patients, June-August 2020, Lagos, Nigeria
Authors: Shorunke Folajimi O. , Okolocha Emmanuel C. , Kia Grace S. , Usman Aishat , Akano Oluseyi , Awosanya Emmanuel J.
Published: March 2022

Background

Lagos State is the epicenter of COVID-19 in Nigeria, having the highest number of cases and death. Veterinary practitioners play an important role in public health and risk exposure to SARS-CoV-2, the virus that causes COVID-19 while attending to animal patients and owners. We determined the prevalence of covid-19 among veterinary practitioners and their dog patients in Lagos, and the associated risk factors during the lockdown.

Methods

We administered questionnaires, reviewed clinical records and conducted serological test to determine the COVID-19 status of 112 veterinary practitioners and 154 dog patients and to assess the associated factors in nine veterinary clinics or hospitals between June to August 2020. Data were analyzed using descriptive statistics, bivariate and multivariate analyses at 5% significant level.

Result

The mean age of participants was 37.5±10.5 and 66 (58.9%) were male. COVID-19 cases among the veterinary practitioners and dogs were 29 (25.9%) and 3 (2%), respectively. Predictors of COVID-19 cases among veterinary practitioners were contact with a SARS-CoV-2 infected dog (AOR: 25.42; CI 4.73-136.66); being a veterinary doctor working during the lockdown (AOR: 6.11; CI 1.56-24.00) and not disinfecting examination table after attending to dogs (AOR: 12.43; CI 1.39-110.99).

Conclusion

Veterinary practitioners and dogs in Lagos were exposed to SARS-COV-2 virus during the COVID-19 lockdown. Contact with SARS-CoV-2 infected dogs, being a veterinary doctor working during the lockdown and not disinfecting examination tables after clinical examination were predictors of COVID-19 cases among veterinary practitioners in Lagos State. Strict Infection, Prevention and Control measures are recommended in veterinary practice.
Feasibility of non-invasive recording of somatosensory evoked potential in pigs
Authors: Hoareau Guillaume L. , Peters Angela , Hilgart David , Iversen Marta , Clark Gregory , Zabriskie Matthew , Rieke Viola , Floyd Candace , Shah Lubdha
Published: March 2022

Background

Non-invasive measurement of somatosensory-evoked potentials (SEP) in a large animal model is important to translational cognitive research. We sought to develop a methodology for neurophysiological recording via a transcranial electroencephalography (EEG) cap under an effective sedative regimen with dexmedetomidine, midazolam, and butorphanol that will produce sedation instead of anesthesia while not compromising data quality.

Results

Pigs received intramuscular dexmedetomidine, midazolam, and butorphanol for SEP assessment with peroneal nerve stimulation. Semi-quantitative sedation assessment was performed after the animal was sufficiently sedated and 30 min later, during the transcranial SEP recording. SEP data were analyzed with commercial software. Binary qualitative analysis of the recording was categorized by an experienced neurophysiologist. All four animals had adequate surface SEP recordings. Animals received 43 [21–47] mcg/kg of dexmedetomidine, 0.3 [0.2–0.3] mg/kg of midazolam, and 0.3 [0.3–0.3] mg/kg of butorphanol IM. All treatments resulted in moderate to deep sedation (Baseline median sedation score 11.5 [11–12]; median score at 30 min: 11.5 [10.5–12]). Heart rate (median [range]) (55 [49–71] beats per minute), respiratory rate (24 [21–30] breaths per minute), and hemoglobin oxygen saturation (99 [98–100]%) and body temperature (37.7 [37.4–37.9] °C) remained within clinically acceptable ranges. There were no undesirable recovery incidents.

Conclusions

In this pilot study, we demonstrate the feasibility of SEP recording via a transcranial EEG cap under an effective sedative regimen in pigs. Our approach will expand the use of a large animal model in neurotranslational research.
MEN4, the MEN1 Mimicker: A Case Series of three Phenotypically Heterogenous Patients With Unique CDKN1B Mutations
Authors: Seabrook Amanda , Wijewardene Ayanthi , De Sousa Sunita , Wong Tang , Sheriff Nisa , Gill Anthony J , Iyer Rakesh , Field Michael , Luxford Catherine , Clifton-Bligh Roderick , McCormack Ann , Tucker Katherine
Published: March 2022

Context

Germline CDKN1B pathogenic variants result in multiple endocrine neoplasia type 4 (MEN4), an autosomal dominant hereditary tumor syndrome variably associated with primary hyperparathyroidism, pituitary adenoma, and duodenopancreatic neuroendocrine tumors.

Objective

To report the phenotype of 3 unrelated cases each with a unique germline CDKN1B variant (of which 2 are novel) and compare these cases with those described in the current literature.

Design/Methods

Three case studies, including clinical presentation, germline, and tumor genetic analysis and family history.

Setting

Two tertiary University Hospitals in Sydney, New South Wales, and 1 tertiary University Hospital in Canberra, Australian Capital Territory, Australia.

Outcome

Phenotype of the 3 cases and their kindred; molecular analysis and tumor p27kip1 immunohistochemistry.

Results

Family A: The proband developed multiglandular primary hyperparathyroidism, a microprolactinoma and a multifocal nonfunctioning duodenopancreatic neuroendocrine tumor. Family B: The proband was diagnosed with primary hyperparathyroidism from a single parathyroid adenoma. Family C: The proband was diagnosed with a nonfunctioning pituitary microadenoma and ectopic Cushing’s syndrome from an atypical thymic carcinoid tumor. Germline sequencing in each patient identified a unique variant in CDKN1B, 2 of which are novel (c.179G > A, p.Trp60*; c.475G > A, p.Asp159Asn) and 1 previously reported (c.374_375delCT, p.Ser125*).

Conclusions

Germline CDKN1B pathogenic variants cause the syndrome MEN4. The phenotype resulting from the 3 pathogenic variants described in this series highlights the heterogenous nature of this syndrome, ranging from isolated primary hyperparathyroidism to the full spectrum of endocrine manifestations. We report the first described cases of a prolactinoma and an atypical thymic carcinoid tumor in MEN4.
Restoration of DNA integrity and the cell cycle by electric stimulation in planarian tissues damaged by ionizing radiation
Authors: Davidian Devon , LeGro Melanie , Barghouth Paul G. , Rojas Salvador , Ziman Benjamin , Maciel Eli Isael , Ardell David , Escobar Ariel L. , Oviedo Néstor J.
Published: March 2022

Exposure to high levels of ionizing γ radiation leads to irreversible DNA damage and cell death. Here, we establish that exogenous application of electric stimulation enables cellular plasticity and the re-establishment of stem cell activity in tissues damaged by ionizing radiation. We show that subthreshold direct current stimulation (DCS) rapidly restores pluripotent stem cell populations previously eliminated by lethally γ-irradiated tissues of the planarian flatworm Schmidtea mediterranea. Our findings reveal that DCS enhances DNA repair, transcriptional activity, and cell cycle entry in post-mitotic cells. These responses involve rapid increases in cytosolic Ca2+ concentration through the activation of L-type Cav channels and intracellular Ca2+ stores, leading to the activation of immediate early genes and ectopic expression of stem cell markers in post-mitotic cells. Overall, we show the potential of electric current stimulation to reverse the damaging effects of high-dose γ radiation in adult tissues. Furthermore, our results provide mechanistic insights describing how electric stimulation effectively translates into molecular responses capable of regulating fundamental cellular functions without the need for genetic or pharmacological intervention.
Leg Dominance Does Not Influence Maximal Force, Force Steadiness, or Motor Unit Discharge Characteristics
Authors: PETROVIC IVANA , AMIRIDIS IOANNIS G. , HOLOBAR ALES , TRYPIDAKIS GEORGIOS , KELLIS ELEFTHERIOS , ENOKA ROGER M.
Published: March 2022

Purpose

The aim of our study was to compare maximal force, force steadiness, and discharge characteristics of motor units in tibialis anterior during contractions with the dorsiflexors of the dominant and nondominant legs at low-to-moderate target forces and three ankle angles.

Methods

Twenty young adults performed maximal and submaximal isometric contractions (5%, 10%, 20%, 40%, and 60% of maximal voluntary contraction (MVC)) with the dorsiflexors of the dominant and nondominant legs at three ankle angles (75°, short length; 90°, intermediate length; 105°, long length). High-density EMG signals from the tibialis anterior muscle of each leg were recorded.

Results

Maximal force (average dominant, 182.9 ± 64.5 N; nondominant, 179.0 ± 58.8 N) and the fluctuations in force, quantified as absolute (SD) and normalized amplitudes (coefficient of variation (CoV)), were similar between the two legs across the three ankle angles (average CoV for dominant, 1.5% ± 1.0%; nondominant, 1.7% ± 1.3%). The CoV for force for both legs decreased from 5% to 20% MVC force, and then it plateaued at 40% and 60% MVC force. EMG amplitude, mean discharge rate of motor units, discharge variability (interspike interval), and the variability in neural drive (filtered cumulative spike train) were similar between the two legs across the submaximal contractions.

Conclusions

MVC force and force steadiness were similar across ankle angles and target forces between the dominant and nondominant legs. The attributes that underlie the self-reported identification of a dominant leg were not associated with the force capacity or the control of force for the dorsiflexor muscles, at least during isometric contractions.
Early Changes of Hamstrings Morphology and Contractile Properties during 10 d of Complete Inactivity
Authors: FRANCHI MARTINO V. , SARTO FABIO , SIMUNIČ BOŠTIAN , PIŠOT RADO , NARICI MARCO V.
Published: March 2022

Purpose

The hamstrings (HS) muscle group plays a fundamental role in maintaining knee stability, thus contributing to the prevention and rehabilitation of lower limb musculoskeletal injuries. However, little is known about HS structural and functional adaptations after periods of prolonged inactivity. Our purpose was to investigate the HS morphological and contractile properties changes during 10 d of bed rest (BR).

Methods

Ten young healthy males underwent a 10-d BR. HS cross-sectional area (CSA) (at 30%, 50%, and 70% of femur length) and biceps femoris long head (BFlh) architecture were assessed by ultrasound imaging after 0 d (BR0), 2 d (BR2), 4 d (BR4), 6 d (BR6), and 10 d (BR10) of BR, whereas BFlh contractile properties (radial twitch displacement [Dm] and contraction time [Tc]) were evaluated at the same time points by tensiomyography. HS muscle volume was assessed by magnetic resonance imaging at BR0 and BR10.

Results

A reduction in muscle volume was observed in BFlh (P = 0.002; Δ = −3.53%), biceps femoris short head (P = 0.002; Δ = −3.54%), semitendinosus (P = 0.002; Δ = −2.63%), semimembranosus (P = 0.002; Δ = −2.01%), and HS pooled together (P < 0.001; Δ = −2.78%). Early changes in CSA were detected at 30% femur length already at BR6 for BFlh (P = 0.009; Δ = −2.66%) and biceps femoris short head (P = 0.049; Δ = −1.96%). We also found a reduction in fascicle length at BR6 (P = 0.035; Δ = −2.44%) and BR10 (P < 0.001; Δ = −2.84%). Dm and Tc increased at BR2 (P = 0.010; Δ = 30.0%) and B10 (P = 0.019; Δ = 19.7%), respectively.

Conclusions

Despite being a nonpostural muscle group, HS exhibited a moderate reduction in muscle dimensions in response to a short unloading period. Small changes in BFlh fascicle length were also observed, accompanied by alterations in BFLh contractile properties. These HS modifications should not be ignored from a clinical perspective.
A Contractualist Defense of Sweatshop Regulation
Authors: Kuyumcuoglu Huseyin
Published: March 2022

Kates argues that ex ante contractualism fails to defend interference with sweatshops on moral grounds. In this commentary, I argue that Kates does not apply this approach correctly. Ex ante contractualism, indeed, successfully defends interference and thus should still be considered an appealing alternative to other moral approaches for evaluating when and how to interfere in sweatshop conditions to help workers.
Trial-Period Technostress: A Conceptual Definition and Mixed-Methods Investigation
Authors: Maier Christian , Laumer Sven , Thatcher Jason Bennett , Wirth Jakob , Weitzel Tim
Published: March 2022

Application abstract:

A large number of electronic devices are rejected and returned to the seller in the first weeks of trial use, which costs organizations millions of dollars. We aimed to identify the causes behind those returns and find that stress during the trial period is a major contributing factor. Users are stressed as they need to learn how to use the electronic device, integrate it into their daily life, and take care of privacy issues. All that creates stress and makes users feel unhappy with using the electronic device so that they will send it back to the seller. In particular, we see in our results that individuals who are not innovative in using IT in general and have a low willingness to learn using the new electronic device tend to send back electronic devices in the first weeks of the trial period. When discussing those results with individuals who had sent back tablet devices, we see that stress in the trial period can even overwhelm positive thoughts. So, with our results, we conclude that stress in the trial period has many causes that are often responsible for returning electronic devices.
Optimal Picking Policies in E-Commerce Warehouses
Authors: Schiffer Maximilian , Boysen Nils , Klein Patrick S. , Laporte Gilbert , Pavone Marco
Published: March 2022

In e-commerce warehouses, online retailers increase their efficiency by using a mixed-shelves (or scattered storage) concept, where unit loads are purposefully broken down into single items, which are individually stored in multiple locations. Irrespective of the stock keeping units a customer jointly orders, this storage strategy increases the likelihood that somewhere in the warehouse the items of the requested stock keeping units will be in close vicinity, which may significantly reduce an order picker’s unproductive walking time. This paper optimizes picker routing through such mixed-shelves warehouses. Specifically, we introduce a generic exact algorithmic framework that covers a multitude of picking policies, independently of the underlying picking zone layout, and is suitable for real-time applications. This framework embeds a bidirectional layered graph algorithm that provides the best known performance for the simple picking problem with a single depot and no further attributes. We compare three different real-world e-commerce warehouse settings that differ slightly in their application of scattered storage and in their picking policies. Based on these, we derive additional layouts and settings that yield further managerial insights. Our results reveal that the right combination of drop-off points, dynamic batching, the utilization of picking carts, and the picking zone layout can greatly improve the picking performance. In particular, some combinations of policies yield efficiency increases of more than 30% compared with standard policies currently used in practice.

This paper was accepted by Chung Piaw Teo, optimization.
Managing Self-Confidence: Theory and Experimental Evidence
Authors: Möbius Markus M. , Niederle Muriel , Niehaus Paul , Rosenblat Tanya S.
Published: March 2022

We use a series of experiments to understand whether and how people’s beliefs about their own abilities are biased relative to the Bayesian benchmark and how these beliefs then affect behavior. We find that subjects systematically and substantially overweight positive feedback relative to negative (asymmetry) and also update too little overall (conservatism). These biases are substantially less pronounced in an ego-free control experiment. Updating does retain enough of the structure of Bayes’ rule to let us model it coherently in an optimizing framework, in which, interestingly, asymmetry and conservatism emerge as complementary biases. We also find that exogenous changes in beliefs affect subjects’ decisions to enter into a competition and do so similarly for more and less biased subjects, suggesting that people cannot “undo” their biases when the time comes to decide.

This paper was accepted by Axel Ockenfels, behavioral economics and decision analysis.

Funding: Financial support from the National Science Foundation (NSF), Harvard University, and Wesleyan University is gratefully acknowledged. P. Niehaus received financial support from an NSF Graduate Research Fellowship.

Supplemental Material: The data files are available at https://doi.org/10.1287/mnsc.2021.4294 .
The Impact of Bribery Relationships on Firm Growth in Transition Economies
Authors: Jung Hyun Ju , Lee Seung-Hyun
Published: March 2022

This study explores how bribery affects firm growth by focusing on the asymmetric dependence of firms on government resources and services. We conceptualize bribery as relationships through which bribery requests require firms to frequently interact with rent-seeking government officials. Through bribery relationships, such officials extort firms beyond the exchange of bribe money for preferential treatment, depriving acquiescing firms of time and effort and thereby imposing hidden costs that could be otherwise used for firm growth. We find that bribery relationships damage firm growth. Firm status such as introducing new products or not affects how rent-seeking government officials check on firms and calculate their extortion schemes in bribery relationships; bribery relationships damage firm growth more significantly for firms without new products. The damage of bribery relationships to firm growth is also contingent on institutional environments. Under pervasive corruption, firms in bribery relationships may increase their acquiescence to the extortion of rent-seeking government officials. In countries with high-quality governance, however, firms can depend on sound regulations and rules of law and government officials experience high moral costs of corruption. Thus, the negative effect of the bribery relationship on firm growth will be strengthened under pervasive corruption and weakened under high-quality governance. Using Business Environment and Enterprise Performance Survey and World Governance Indicators data for 28 Eastern European countries from 2002–2014, we demonstrate the multifaceted features of the bribery relationship and its interaction with country-level institutional environments.

Supplemental Material: The online appendices are available at https://doi.org/10.1287/orsc.2022.1575 .
Primary biliary cholangitis: advances in understanding and management
Authors: Smith Alex , Giles Benjamin , Aspinall Richard J
Published: March 2022

Recent years have seen major advances in our understanding of primary biliary cholangitis, with the condition now renamed to reflect the majority of patients who do not have cirrhosis. Data from large multicentre studies have greatly increased our knowledge of the natural history of primary biliary cholangitis, making the identification of higher risk patients clearer and facilitating the development of new medications. Recent guidelines have emphasised the importance of risk stratification, targeted treatment of symptoms and early prioritisation for second line therapies. The review summarises recent major developments in our understanding of primary biliary cholangitis and its management.
The newest bio-based composites are made from your garbage
Authors: Bigio Tato , Marziparo Gabriela
Published: March 2022

Tato Bigio, co-CEO and co-founder, UBQ Materials and Gabriela Marziparo, global business development manager, Polyram Group, discuss the benefits of bio-based composites made from household waste.
Informal housing and residents’ well-being in Caracas and Sydney: a comparative study of residents’ experiences
Authors: Quintana Vigiola Gabriela
Published: March 2022

Informal housing has been assessed to have a negative impact on its residents’ well-being. However, this article demonstrates that residents also perceive and experience some positive effects within their precarious housing condition. Both the Global South and the Global North are home to informal housing, yet there are very few studies that compare these contexts. In response, this article discusses the differences and similarities between how informality and precarious housing emerges and is experienced by its residents in both contexts. Qualitative content analysis was applied to interpret the data collected in two separate studies developed in Caracas and Sydney. The perspectives of two different populations deemed vulnerable, low-income groups are discussed: slum dwellers and international students. Aligning with Roy’s (Roy, 2005) proposition in the literature about the need to include actors such as residents in the discussion on informality, this research approach was applied to delve into the accounts of the participants to understand their meanings and experiences in the production of, access to and their everyday lives in their housing environments. Four themes arose from the interpretation of the participants’ accounts: (1) the production of informal housing; (2) permanency versus temporality; (3) networks and relationships; and (4) the overall impact on residents’ everyday lives and well-being. These emerged as significant themes for understanding the perceived well-being of informal housing residents. Residents’ experiences in the Global North and South are indeed different. However, despite the oppressing external conditions and their vulnerability, people in both areas implement psychosocial and physical strategies to improve their housing conditions and well-being. By acknowledging and understanding people’s experiences of informal housing – including those of a positive nature – we gain a deeper comprehension of the processes influencing residents’ well-being.
A decisive moment: human rights or authoritarianism? It is a choice
Authors: Kjaerum Morten
Published: March 2022

The VUCA is a well-known business concept capturing that we live in an ever changing global and local landscape defined by volatility, uncertainty, complexity and ambiguity. The convergence of profound changes brought about by new technologies and global crisis such as the Covid-19 pandemic and the NATO defeat in Afghanistan constitute the root of the VUCA world. With the outset in these two contemporary crises I will explore what sort of change and lessons learned can be derived from what they caused. This historically defining moment may be the time where human rights are either marginalized for a long period of time or they take another step forward realizing the interconnectedness and interrelatedness of all rights in addressing global in-equalities.
The place and potential of crisis/crises in critical studies on men and masculinities
Authors: Hearn Jeff
Published: March 2022

This article derives from considering the interrelations of two sets of long-term international work: that on interdisciplinary crisis studies and that on critical studies on men and masculinities. More specifically, it interrogates the place and potential of crisis and crises in the politics and problematics of men and masculinities, including how crisis can be a driver of critical studies on men and masculinities. Further to this, four main forms of deployment of crisis within critical studies on men and masculinities are interrogated. There is a well-elaborated debate on what has come to be called ‘the crisis of masculinity’. Interestingly, this takes very different shapes, sometimes even opposite constructions, in different parts of the world and within different discourses. Even with this diversity, crisis is often presented as ‘fact’, identity and a result of ‘role confusion’ for boys, young men and men around what it might mean to be a boy and man in contemporary times. This approach contrasts with those foregrounding more endogenous crisis tendencies, first, within patriarchal relations and then of gender itself, with associated deconstructions of men and masculinity. Meanwhile, within critical studies on men and masculinities, there has been a relative neglect, at least until recently, of large-scale global crises. Key examples include financial crisis, political crisis, ecological crisis and pandemic crisis. In short, there appears to have been over-recognition of the ‘crisis of masculinity’, some recognition of crisis tendencies of patriarchal relations and of gender, and under-recognition of crises created or reinforced largely by certain men and masculinities globally and transnationally.
Slow crisis in Bissau and beyond
Authors: Vigh Henrik
Published: March 2022

This article takes an ethnographic look at processes of long-term and lingering crises. Building on longitudinal and transnational fieldwork with migrants from Bissau, the capital of Guinea-Bissau, it illuminates the ways that crisis may ramify across time and scale, thereby affecting everyday life, social relations and political dynamics. While the concept of ‘slow crisis’ sits uncomfortably within our common understanding of crisis as a momentary aberration and tipping point, the article clarifies how attending to the lingering and wandering effects of the phenomenon may grant us a fuller understanding of its temporality and social life. The article explores the way crisis is lived through a longitudinal study of Guinea-Bissauan migrants in Bissau, Lisbon and Paris. Via an ethnographic case study of a protracted and compound crisis, it illuminates the social deterioration, contraction and fragmentation that define such situations, and points to the common dynamics of crises as continuing critical conditions rather than singular aberrations.
Foundations of circadian medicine
Authors: Kramer Achim , Lange Tanja , Spies Claudia , Finger Anna-Marie , Berg Daniela , Oster Henrik
Published: March 2022

The circadian clock is an evolutionarily highly conserved endogenous timing program that structures physiology and behavior according to the time of day. Disruption of circadian rhythms is associated with many common pathologies. The emerging field of circadian medicine aims to exploit the mechanisms of circadian physiology and clock–disease interaction for clinical diagnosis, treatment, and prevention. In this Essay, we outline the principle approaches of circadian medicine, highlight the development of the field in selected areas, and point out open questions and challenges. Circadian medicine has unambiguous health benefits over standard care but is rarely utilized. It is time for clock biology to become an integrated part of translational research.
Cortical softening elicits zygotic contractility during mouse preimplantation development
Authors: Özgüç Özge , de Plater Ludmilla , Kapoor Varun , Tortorelli Anna Francesca , Clark Andrew G. , Maître Jean-Léon
Published: March 2022

Actomyosin contractility is a major engine of preimplantation morphogenesis, which starts at the 8-cell stage during mouse embryonic development. Contractility becomes first visible with the appearance of periodic cortical waves of contraction (PeCoWaCo), which travel around blastomeres in an oscillatory fashion. How contractility of the mouse embryo becomes active remains unknown. We have taken advantage of PeCoWaCo to study the awakening of contractility during preimplantation development. We find that PeCoWaCo become detectable in most embryos only after the second cleavage and gradually increase their oscillation frequency with each successive cleavage. To test the influence of cell size reduction during cleavage divisions, we use cell fusion and fragmentation to manipulate cell size across a 20- to 60-μm range. We find that the stepwise reduction in cell size caused by cleavage divisions does not explain the presence of PeCoWaCo or their accelerating rhythm. Instead, we discover that blastomeres gradually decrease their surface tensions until the 8-cell stage and that artificially softening cells enhances PeCoWaCo prematurely. We further identify the programmed down-regulation of the formin Fmnl3 as a required event to soften the cortex and expose PeCoWaCo. Therefore, during cleavage stages, cortical softening, mediated by Fmnl3 down-regulation, awakens zygotic contractility before preimplantation morphogenesis.
Ten simple rules for finding and selecting R packages
Authors: Wendt Caroline J. , Anderson G. Brooke
Published: March 2022

R is an increasingly preferred software environment for data analytics and statistical computing among scientists and practitioners. Packages markedly extend R’s utility and ameliorate inefficient solutions to data science problems. We outline 10 simple rules for finding relevant packages and determining which package is best for your desired use. We begin in Rule 1 with tips on how to consider your purpose, which will guide your search to follow, where, in Rule 2, you’ll learn best practices for finding and collecting options. Rules 3 and 4 will help you navigate packages’ profiles and explore the extent of their online resources, so that you can be confident in the quality of the package you choose and assured that you’ll be able to access support. In Rules 5 and 6, you’ll become familiar with how the R Community evaluates packages and learn how to assess the popularity and utility of packages for yourself. Rules 7 and 8 will teach you how to investigate and track package development processes, so you can further evaluate their merit. We end in Rules 9 and 10 with more hands-on approaches, which involve digging into package code.
Fast protein structure comparison through effective representation learning with contrastive graph neural networks
Authors: Xia Chunqiu , Feng Shi-Hao , Xia Ying , Pan Xiaoyong , Shen Hong-Bin
Published: March 2022

Protein structure alignment algorithms are often time-consuming, resulting in challenges for large-scale protein structure similarity-based retrieval. There is an urgent need for more efficient structure comparison approaches as the number of protein structures increases rapidly. In this paper, we propose an effective graph-based protein structure representation learning method, GraSR, for fast and accurate structure comparison. In GraSR, a graph is constructed based on the intra-residue distance derived from the tertiary structure. Then, deep graph neural networks (GNNs) with a short-cut connection learn graph representations of the tertiary structures under a contrastive learning framework. To further improve GraSR, a novel dynamic training data partition strategy and length-scaling cosine distance are introduced. We objectively evaluate our method GraSR on SCOPe v2.07 and a new released independent test set from PDB database with a designed comprehensive performance metric. Compared with other state-of-the-art methods, GraSR achieves about 7%-10% improvement on two benchmark datasets. GraSR is also much faster than alignment-based methods. We dig into the model and observe that the superiority of GraSR is mainly brought by the learned discriminative residue-level and global descriptors. The web-server and source code of GraSR are freely available at www.csbio.sjtu.edu.cn/bioinf/GraSR/ for academic use.
Co-production of knowledge as part of a OneHealth approach to better control zoonotic diseases
Authors: Asaaga Festus A. , Young Juliette C. , Srinivas Prashanth N. , Seshadri Tanya , Oommen Meera A. , Rahman Mujeeb , Kiran Shivani K. , Kasabi Gudadappa S. , Narayanaswamy Darshan , Schäfer Stefanie M. , Burthe Sarah J. , August Tom , Logie Mark , Chanda Mudassar M. , Hoti Subhash L. , Vanak Abi T. , Purse Bethan V.
Published: March 2022

There is increased global and national attention on the need for effective strategies to control zoonotic diseases. Quick, effective action is, however, hampered by poor evidence-bases and limited coordination between stakeholders from relevant sectors such as public and animal health, wildlife and forestry sectors at different scales, who may not usually work together. The OneHealth approach recognises the value of cross-sectoral evaluation of human, animal and environmental health questions in an integrated, holistic and transdisciplinary manner to reduce disease impacts and/or mitigate risks. Co-production of knowledge is also widely advocated to improve the quality and acceptability of decision-making across sectors and may be particularly important when it comes to zoonoses. This paper brings together OneHealth and knowledge co-production and reflects on lessons learned for future OneHealth co-production processes by describing a process implemented to understand spill-over and identify disease control and mitigation strategies for a zoonotic disease in Southern India (Kyasanur Forest Disease). The co-production process aimed to develop a joint decision-support tool with stakeholders, and we complemented our approach with a simple retrospective theory of change on researcher expectations of the system-level outcomes of the co-production process. Our results highlight that while co-production in OneHealth is a difficult and resource intensive process, requiring regular iterative adjustments and flexibility, the beneficial outcomes justify its adoption. A key future aim should be to improve and evaluate the degree of inter-sectoral collaboration required to achieve the aims of OneHealth. We conclude by providing guidelines based on our experience to help funders and decision-makers support future co-production processes.
Experiences of multimorbidity in urban and rural Malawi: An interview study of burdens of treatment and lack of treatment
Authors: Chikumbu Edith F. , Bunn Christopher , Kasenda Stephen , Dube Albert , Phiri-Makwakwa Enita , Jani Bhautesh D. , Jobe Modu , Wyke Sally , Seeley Janet , Crampin Amelia C. , Mair Frances S. ,   on behalf of the MAfricaEE Project
Published: March 2022

Multimorbidity (presence of ≥2 long term conditions (LTCs)) is a growing global health challenge, yet we know little about the experiences of those living with multimorbidity in low- and middle-income countries (LMICs). We therefore explore: 1) experiences of men and women living with multimorbidity in urban and rural Malawi including their experiences of burden of treatment and 2) examine the utility of Normalization Process Theory (NPT) and Burden of Treatment Theory (BOTT) for structuring analytical accounts of these experiences. We conducted in depth, semi-structured interviews with 32 people in rural (n= 16) and urban settings (n= 16); 16 males, 16 females; 15 under 50 years; and 17 over 50 years. Data were analysed thematically and then conceptualised through the lens of NPT and BOTT. Key elements of burden of treatment identified included: coming to terms with and gaining an understanding of life with multimorbidity; dealing with resulting disruptions to family life; the work of seeking family and community support; navigating healthcare systems; coping with lack of continuity of care; enacting self-management advice; negotiating medical advice; appraising treatments; and importantly, dealing with the burden oflackof treatments/services. Poverty and inadequate healthcare provision constrained capacity to deal with treatment burden while supportive social and community networks were important enabling features. Greater access to health information/education would lessen treatment burden as would better resourced healthcare systems and improved standards of living. Our work demonstrates the utility of NPT and BOTT for aiding conceptualisation of treatment burden issues in LMICs but our findings highlight that ‘lack’ of access to treatments or services is an important additional burden which must be integrated in accounts of treatment burden in LMICs.
Testing availability, positioning, promotions, and signage of healthier food options and purchasing behaviour within major UK supermarkets: Evaluation of 6 nonrandomised controlled intervention studies
Authors: Piernas Carmen , Harmer Georgina , Jebb Susan A.
Published: March 2022

Background

Governments are increasingly looking for policies to change supermarket environments to support healthier food purchasing. We evaluated 6 interventions within major United Kingdom grocery stores, including availability, positioning, promotions, and signage strategies to encourage selection of healthier products.

Methods and findings

Nonrandomised controlled study designs were used, except for one intervention that was rolled out nationwide using a pre/post within-store design. Store-level weekly sales (units, weight (g), and value (£)) of products targeted in the interventions were used in primary analyses using multivariable hierarchical models and interrupted time series (ITS) analyses.

Stocking low fat chips next to regular chips was associated with decreases in sales of regular chips (units) in intervention versus control stores (−23% versus −4%; P = 0.001) with a significant level change in ITS models (P = 0.001). Increasing availability of lower energy packs of biscuits was associated with increased sales but reduced sales of regular biscuits in intervention versus control stores (lower energy biscuits +18% versus −2%; P = 0.245; regular biscuits −4% versus +7%; P = 0.386), although not significantly, though there was a significant level change in ITS models (P = 0.004 for regular biscuits). There was no evidence that a positioning intervention, placing higher fibre breakfast cereals at eye level was associated with increased sales of healthier cereal or reduced sales of regular cereal. A price promotion on seasonal fruits and vegetables showed no evidence of any greater increases in sales of items on promotion in intervention versus control stores (+10% versus +8%; P = 0.101) but a significant level change in ITS models (P < 0.001). A nationwide promotion using Disney characters was associated with increased sales of nonsugar baked beans (+54%) and selected fruits (+305%), with a significant level change in ITS models (P < 0.001 for both). Shelf labels to highlight lower sugar beverages showed no evidence of changes in purchasing of lower or higher sugar drinks. These were all retailer-led interventions that present limitations regarding the lack of randomisation, residual confounding from unmeasured variables, absolute differences in trends and sales between intervention versus control stores, and no independent measures of intervention fidelity.

Conclusions

Increasing availability and promotions of healthier alternatives in grocery stores may be promising interventions to encourage purchasing of healthier products instead of less healthy ones. There was no evidence that altering positioning within an aisle or adding shelf edge labelling is associated with changes in purchasing behaviours.

Trial registration

https://osf.io/br96f/.
Utilisation of semiconductor sequencing for the detection of predictive biomarkers in glioblastoma
Authors: Williams Gareth , Llewelyn Alexander , Thatcher Robert , Hardisty Keeda-Marie , Loddo Marco
Published: March 2022

The standard treatment for glioblastoma involves a combination of surgery, radiation and chemotherapy but have limited impact on survival. The exponential increase in targeted agents directed at pivotal oncogenic pathways now provide new therapeutic opportunities for this tumour type. However, lack of comprehensive precision oncology testing at diagnosis means such therapeutic opportunities are potentially overlooked. To investigate the role of semiconductor sequencing for detection of predictive biomarkers in routine glioblastoma samples we have undertaken analysis of test trending data generated by a clinically validated next generation sequencing platform designed to capture actionable genomic variants distributed across 505 genes. Analysis was performed across a cohort of 55 glioblastoma patients. Analysis of trending data has revealed a complex and rich actionable mutational landscape in which 166 actionable mutations were detected across 36 genes linked to 17 off label targeted therapy protocols and 111 clinical trials. The majority of patients harboured three or more actionable mutations affecting key cancer related regulatory networks including the PI3K/AKT/MTOR and RAS/RAF/MEK/MAPK signalling pathways, DNA-damage repair pathways and cell cycle checkpoints. Linkage with immunotherapy and PARP inhibitors was identified in 44% of glioblastoma patients as a consequence of alterations in DNA-damage repair genes. Taken together our data indicates that precision oncology testing utilising semiconductor sequencing can be used to identify a broad therapeutic armamentarium of targeted therapies and immunotherapies that can be potentially employed for the improved clinical management of glioblastoma patients.
Molecular dynamics study on the effects of charged amino acid distribution under low pH condition to the unfolding of hen egg white lysozyme and formation of beta strands
Authors: Zein Husnul Fuad , Alam Ibrar , Asanithi Piyapong , Sutthibutpong Thana
Published: March 2022

Aggregation of unfolded or misfolded proteins into amyloid fibrils can cause various diseases in humans. However, the fibrils synthesized in vitro can be developed toward useful biomaterials under some physicochemical conditions. In this study, atomistic molecular dynamics simulations were performed to address the mechanism of beta-sheet formation of the unfolded hen egg-white lysozyme (HEWL) under a high temperature and low pH. Simulations of the protonated HEWL at pH 2 and the non-protonated HEWL at pH 7 were performed at the highly elevated temperature of 450 K to accelerate the unfolding, followed by the 333 K temperature to emulate some previous in vitro studies. The simulations showed that HEWL unfolded faster, and higher beta-strand contents were observed at pH 2. In addition, one of the simulation replicas at pH 2 showed that the beta-strand forming sequence was consistent with the ‘K-peptide’, proposed as the core region for amyloidosis in previous experimental studies. Beta-strand formation mechanisms at the earlier stage of amyloidosis were explained in terms of the radial distribution of the amino acids. The separation between groups of positively charged sidechains from the hydrophobic core corresponded to the clustering of the hydrophobic residues and beta-strand formation.