bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple predictive biomarker testing in melanoma: Another challenge in identifying the optimal approach on cytological samples
Authors: Iaccarino Antonino , Nacchio Mariantonia , Acanfora Gennaro , Pisapia Pasquale , Malapelle Umberto , Bellevicine Claudio , Troncone Giancarlo , Vigliar Elena
Published: January 2023

Background

The management of cutaneous melanoma has changed dramatically in recent years thanks to the development of tyrosine kinase and immune‐checkpoint inhibitors (ICIs). Thus, multiple biomarker testing is becoming ever more important for the identification of patients who are potentially eligible for these treatments. One reliable approach to the molecular evaluation of metastatic melanoma is fine needle cytology (FNC). To examine the utility of this approach for assessing PD‐L1 expression levels, we evaluated the cellular adequacy of residual cell block (CB) material from metastatic melanomas that were previously tested for BRAF and NRAS mutations.

Methods

We retrieved from our internal archives a series of FNC samples of metastatic melanoma that had been subjected to molecular testing on residual CB material or a dedicated needle rinse between January 2016 and July 2022. Real‐time polymerase chain reaction was used to assess BRAF and NRAS status, and an SP263 assay was employed to ascertain PD‐L1 expression levels.

Results

Overall, n = 19 cases were selected. Of these, 11 (57.9%) cases revealed a BRAF exon 15 p.V600E mutation, one case (5.3%) revealed NRAS mutation, and seven cases (36.8%) showed no mutations. Regarding PD‐L1 assessment, 16/19 (84.2%) cases were deemed adequate, meaning they contained at least 100 viable cells.

Conclusions

We highlighted the feasibility of assessing PD‐L1 expression levels in residual CB material from metastatic melanomas previously tested for BRAF and NRAS mutations. Moreover, we pointed out that FNC needle rinses may be an alternative source of nucleic acids for molecular testing, preserving CB material for immunocytochemistry evaluation.
The Affective Dimension Of Epistemic Injustice
Authors: Zembylas Michalinos
Published: January 2023

This essay focuses on the affective dimension of epistemic injustice — specifically, the affective harms and burdens of epistemic injustice on individuals and groups — and examines how pedagogy may help disrupt the affective injustice that epistemic injustice entails. This theorization facilitates the ability to recognize that affective wrongs are not separate from epistemic wrongs but are instead embedded in them. Here, Michalinos Zembylas brings recent philosophical inquiry on affective injustice into conversation with considerations of epistemic injustice in order to discuss how affect‐related conceptions of epistemic injustice help education scholars to illuminate the entanglement of the epistemic and the affective in the wrongs of testimonial, hermeneutical, and other forms of epistemic injustice. His analysis outlines how some theoretical concepts concerning “affective goods” — including affective freedoms, affective resources, and affective recognition — have important pedagogical implications for the role educators can play in rupturing epistemic‐affective injustices.
Rigidoporus microporus and the white root rot disease of rubber
Authors: Saidi Noor Baity , Al‐Obaidi Jameel R. , Fisol Ahmad Faiz bin Che
Published: January 2023

Rigidoporus microporus is an economically important plant pathogenic fungus causing particularly severe losses to the rubber industry worldwide. The pathogen is responsible for white root rot (WRR) disease, infecting the host roots via white fibrous mycelia, causing vascular disfunction, and visible symptoms including leaf discolouration and dieback in severely infected trees. The final stage of the disease is characterized by the appearance of basidiocarps at the tree collar. The development of WRR in rubber plantations is dependent on fungal diversity in the soil, pH, temperature, and cation levels. Several ‘‐omics’ approaches have been undertaken to understand how R. microporus functions with the objective, ultimately, to control WRR. Unfortunately, no resistant rubber clone has been identified to date. The disease is managed through physical and chemical methods that are laborious and negatively impact the environment, respectively. Recent developments in research on R. microporus shed light on potential sustainable routes to WRR disease control using beneficial microorganisms and natural compounds. This review discusses the characteristics of R. microporus isolates from different geographical origins, the pathogenicity and virulence mechanisms of the necrotrophic fungal pathogen, factors that influence the development of WRR, recent findings from the multi‐omics studies, and control methods that are available to combat this economically important pathogen.
Power politics and the expansion of US exports, 1879–1938
Authors: Tena‐Junguito Antonio , Restrepo‐Estrada Maria Isabel
Published: January 2023

In this article, we present quantitative evidence for the first time of the effect of US power politics on the expansion of its export market from the late nineteenth century to the eve of the Second World War. Like other empires, US imperial policy was expressed through annexation, gunboat policies, and asymmetrical trade agreements. We find that US exports to territories that became colonies or protectorates and those involved in other US military interventions grew more than three times faster between 1880–5 and 1934–8 than in the rest of the world. Our most relevant contribution to this discussion relies on a new geographically extensive database with information on bilateral trade flows, market size, trade costs, and variables that capture US political and military power. We first estimate a gravity equation to see the relationship between our power politics variables and US exports. Then, we present causal evidence of the role played by the colonies and protectorates in the expansion of US exports through an event study and the estimation of a generalized difference‐in‐differences model.
A retrospective non‐interventional study evaluating the pharmacokinetic interactions between cenobamate and clobazam
Authors: Elakkary Sally , Hagemann Anne , Klimpel Dennis , Bien Christian G. , Brandt Christian
Published: January 2023

Cenobamate is an antiseizure medication (ASM) approved for the treatment of partial‐onset seizures in adults. As both an inductor and an inhibitor of hepatic enzymes, cenobamate affects the metabolism of other ASMs, among which is clobazam. To our knowledge, the extent of interaction between cenobamate and clobazam and its clinical significance have not been studied yet. In this retrospective study we assessed serum concentrations of clobazam and N‐desmethylclobazam (NCLB)in five patients before and after co‐medication with cenobamate and calculated the percentage increase in concentration‐to‐dose ratio (CDR) of both. We were able to demonstrate that the addition of cenobamate resulted in an increase in serum concentration and consequently in CDR of NCLB in all patients. However this occurred in variable degrees: NCLB concentration showed an increase of 1208 μg/L (CDR145%) in one patient and between 1691 μ/L (CDR 819%) and 3995 μ/L (CDR 1852%) in the other four. This resulted in fatigue, which improved after dose reduction of CLB. Therefore, it is to be concluded that concomitant administration of cenobamate and clobazam can lead to a substantial increase in serum concentrations of NCLB. This can have a positive therapeutic effect on one hand; however, on the other hand, this can lead to unwanted fatigue.
Rational engineering of AA5_2 copper radical oxidases to probe the molecular determinants governing their substrate selectivity
Authors: Koncitikova Radka , Zuily Lisa , Lemarié Emeline , Ribeaucourt David , Saker Safwan , Haon Mireille , Brumer Harry , Guallar Victor , Berrin Jean‐Guy , Lafond Mickael
Published: January 2023

Fungal copper radical oxidases (CROs) from the Auxiliary Activity family 5 (AA5) constitute a group of metalloenzymes that oxidize a wide panel of natural compounds, such as galactose‐containing saccharides or primary alcohols, into product derivatives exhibiting promising biotechnological interests. Despite a well‐conserved first copper‐coordination sphere and overall fold, some members of the AA5_2 subfamily are incapable of oxidizing galactose and galactosides but conversely efficiently catalyse the oxidation of diverse aliphatic alcohols. The objective of this study was to understand which residues dictate the substrate preferences between alcohol oxidases and galactose oxidases within the AA5_2 subfamily. Based on structural differences and molecular modelling predictions between the alcohol oxidase from Colletotrichum graminicola (CgrAlcOx) and the archetypal galactose oxidase from Fusarium graminearum (FgrGalOx), a rational mutagenesis approach was developed to target regions or residues potentially driving the substrate specificity of these enzymes. A set of 21 single and multiple CgrAlcOx variants was produced and characterized leading to the identification of six residues (W39, F138, M173, F174, T246, L302), in the vicinity of the active site, crucial for substrate recognition. Two multiple CgrAlcOx variants, i.e. M4F (W39F, F138W, M173R and T246Q) and M6 (W39F, F138W, M173R, F174Y, T246Q and L302P), exhibited a similar affinity for carbohydrate substrates when compared to FgrGalOx. In conclusion, using a rational site‐directed mutagenesis approach, we identified key residues involved in the substrate selectivity of AA5_2 enzymes towards galactose‐containing saccharides.
HOXB7 induces STAT3‐mediated transformation and lung metastasis in immortalized mammary gland NMuMG cells
Authors: Azuma Kazushi , Sakamoto Mai , Katayama Shota , Matsui Atsuka , Nakamichi Kazuya , Goshima Naoki , Watanabe Shinya , Nakayama Jun , Semba Kentaro
Published: January 2023

The homeobox family genes are often dysregulated in various cancer types. Particularly HOXB7 amplification and overexpression correlate with poor prognosis in various cancer such as gastric, pancreatic, and lung cancers. Moreover, HOXB7 is known to contribute to cancer progression by promoting epithelial to mesenchymal transition, anticancer drug resistance, and angiogenesis. In this study, we show that HOXB7 is coamplified with ERBB2 in a subset of breast cancer patients and HOXB7 expression correlates with poor prognosis in HER2‐positive breast cancer patients. This clinical observation is supported by the following results—HOXB7 overexpression in an immortalized murine mammary gland epithelial cell line NMuMG induces cellular transformation in vitro, tumorigenesis, and lung metastasis through the activation of JAK‐STAT signaling.
Pre‐clinical evidence of a dual NADPH oxidase 1/4 inhibitor (setanaxib) in liver, kidney and lung fibrosis
Authors: Thannickal Victor J. , Jandeleit‐Dahm Karin , Szyndralewiez Cédric , Török Natalie J.
Published: January 2023

Fibrosis describes a dysregulated tissue remodelling response to persistent cellular injury and is the final pathological consequence of many chronic diseases that affect the liver, kidney and lung. Nicotinamide adenine dinucleotide phosphate (NADPH)‐oxidase (NOX) enzymes produce reactive oxygen species (ROS) as their primary function. ROS derived from NOX1 and NOX4 are key mediators of liver, kidney and lung fibrosis. Setanaxib (GKT137831) is a first‐in‐class, dual inhibitor of NOX1/4 and is the first NOX inhibitor to progress to clinical trial investigation. The anti‐fibrotic effects of setanaxib in liver, kidney and lung fibrosis are supported by multiple lines of pre‐clinical evidence. However, despite advances in our understanding, the precise roles of NOX1/4 in fibrosis require further investigation. Additionally, there is a translational gap between the pre‐clinical observations of setanaxib to date and the applicability of these to human patients within a clinical setting. This narrative review critically examines the role of NOX1/4 in liver, kidney and lung fibrosis, alongside the available evidence investigating setanaxib as a therapeutic agent in pre‐clinical models of disease. We discuss the potential clinical translatability of this pre‐clinical evidence, which provides rationale to explore NOX1/4 inhibition by setanaxib across various fibrotic pathologies in clinical trials involving human patients.
Effect of intestinal microbiota on liver disease and its related future prospection: From the perspective of intestinal barrier damage and microbial metabolites
Authors: Jiang Nan , Xiao Yuanyuan , Yuan Kefei , Wang Zhen
Published: January 2023

Liver diseases contribute notably to the global concern of mortality and disease. Emerging evidence has demonstrated that intestinal microbiota can regulate intestinal barrier function and produce bioactive metabolites. Failure of any aspect of this barrier can result in the translocation of microbes into the blood and a sustained inflammatory response that promotes liver injury, fibrosis, and cirrhosis. Here, we review the mechanisms by that intestinal microbiota regulate the intestinal barrier. The multiple underlying mechanisms of intestinal microbiota in liver disease are elaborated in detail, emphasizing them as the bridge linking the liver with gut microbiota. Thus, we highlight the feasibility of targeting the gut‐liver axis for treating liver diseases.
Supply and Demand Effects of Bank Bailouts: Depositors Need Not Apply and Need Not Run
Authors: BERGER ALLEN N. , LAMERS MARTIEN , ROMAN RALUCA A. , SCHOORS KOEN
Published: January 2023

We address two key issues concerning bank bailout effects on depositor and bank behavior. The first is whether bailouts weaken or strengthen market discipline by depositors through deposit supplies. The second is if bailed‐out banks decrease or increase their deposit demands. These questions can only be adequately addressed by analyzing the effects of bailouts on both deposit quantities and prices. We do so for the Troubled Asset Relief Program (TARP) bailouts. Overall, we find that demand changes empirically dominate supply changes, and suggest significantly reduced deposit demand from bailouts. In some cases, however, supply changes dominate and indicate weakened market discipline.
Acute uterine inversion following an induced abortion
Authors: Swarray‐Deen Alim , Oduro Nana E. , Mensah Teresa A. , Boateng Alex K. , Ansing Caesar A. , Coleman Jerry
Published: January 2023

Acute uterine inversion is a rare and potentially life‐threatening obstetric emergency. Its occurrence as a result of a mid‐trimester abortion is an even rarer consequence. We report a case of a 32‐year‐old woman who presented with complete acute uterine inversion and hemorrhagic shock following an incomplete medical abortion at 14 weeks of gestation. Our attempts at non‐operative reversal of the inversion failed. Therefore, we resorted to the manual replacement of the uterus via laparotomy without using surgical instruments or an incision in the cervical ring. The laparotomic manual replacement served as a successful alternative with minimal immediate or long‐term morbidity that may have resulted from trauma and scarring of the uterus.
Sparse hierarchical clustering based on Menopause Rating Scale severity of symptoms collected from perimenopausal and postmenopausal US women in a menopause tablet perceptual efficacy study
Authors: Kuesten Carla , Bi Jian , Zanetti Holiday Durham , Dang Jennifer
Published: January 2023

The sparse hierarchical clustering (SHC) method and the R package “sparcl” are used for consumer segmentation with 247 perimenopausal and postmenopausal US women. The data includes 11 menopause rating scale (MRS) attributes measuring severity of symptoms collected in the first week of a 12‐week extended use menopause tablet perceptual efficacy study. SHC is one of the advanced statistical clustering approaches for high‐dimensional data with potential noise variables. Sparse clustering is an important topic of the actively developing field of statistical learning with sparsity. An advantage of the SHC method is that it simultaneously finds the clusters of subjects and the important clustering variables. It allows clustering the data in low‐dimensional subspaces without dimension reduction of the data before clustering. The SHC method is particularly applicable to consumer segmentation based on high‐dimensional consumer data.

Practical Applications

Sparse hierarchical clustering (SHC) provides advantages in consumer segmentation based on high‐dimensional consumer data with potential noise variables. This advanced clustering method finds the relative importance of attributes in clustering, helping to identify homogeneous clusters and enhance understanding of how consumer responses/needs vary among clusters.
Differences in air displacement plethysmography, bioelectrical impedance analysis and dual‐energy X‐ray absorptiometry for estimating body composition in Chinese children and adolescents
Authors: Huang Yiwen , Wang Xi , Cheng Hong , Dong Hongbo , Shan Xinying , Zhao Xiaoyuan , Wang Xia , Xie Xianghui , Mi Jie
Published: January 2023

Aim

This study aimed to compare body composition (BC) measurements obtained by three widely used BC measuring methods, air displacement plethysmography (ADP), bioelectrical impedance analysis (BIA) and dual‐energy X‐ray absorptiometry (DXA), in Chinese children and adolescents by sex and different BMI categories.

Methods

We used three BC measuring methods to evaluate healthy Chinese children and adolescents aged 5–17 years with BMI categories ranging from underweight to obese. Fat mass (FM, kg), fat mass percentage (FMP, %), fat‐free mass (FFM, kg) and appendicular skeletal muscle mass (ASM, kg) were measured by DXA, BIA and ADP on the same day within 1 h.

Results

A total of 172 Chinese children and adolescents were included in this study. The agreements for FM, FFM and ASM estimated by the three methods were excellent or good at the population level (intraclass correlation coefficient > 0.850, P < 0.05). However, ADP or BIA estimated lower body fat content and higher FFM than DXA (P < 0.001 for all). Moreover, the precise estimates significantly varied across BMI categories. In addition, the limit of agreements was wide, and the differences might not be clinically acceptable at the individual level.

Conclusions

Body fat and FFM obtained by the three commonly used methods were highly correlated, but systematically different and influenced by BMI. This study provided a basis for mutual reference of measurements between three widely used methods.
Hot hand or choking under pressure – Evidence from professional basketball
Authors: Jane Wen‐Jhan
Published: January 2023

This paper examines the existence of a hot hand and whether performing in front of a supportive audience creates a psychological pressure, which may impair performance. Using the task of free throwing in basketball competitions involving National Basketball Association (NBA) regular season and playoff games, I find strong evidence of a hot hand and a negative causal effect of the spectators on the probability of a successful shoot. The results support the hot hand fallacy and are in line with the hypothesis of choking under pressure when performing skill‐based tasks. Furthermore, contrary to what would be expected given the evidence in favor of a choking phenomenon, the effect of star players is insignificant. The hot hand effects for stars and non‐stars are the same in direction. Finally, efforts increase the performance, and the influence of hot hands and choking are not different between home and away shootings.
Organochlorine pesticide residues in water, sediments and Nile tilapia (Oreochromis niloticus) of Lake Nakuru, Kenya and implications for its fishery
Authors: Nantongo Mary Florence , Edebe Joseph , Otachi Elick O. , Kipkemboi Julius
Published: January 2023

The present study was conducted to assess the levels of selected organochlorine pesticide (OCP) residues in water, sediments and Nile tilapia, as well as the potential health risks to humans who consume the fish of Lake Nakuru. Nine composite water and nine sediment samples, as well as 30 fish specimens, were collected from five representative sampling sites within Lake Nakuru. The OCPs targeted in the present study included p,p′‐Dichlorodiphenyl dichloroethane (p,p′‐DDD), p,p′‐dichlorodiphenyldichloroethylene (p,p′‐DDE), p,p′‐dichlorodiphenyltrichloroethane (p,p′‐DDT), heptachlor, heptachlor epoxide, α endosulfan (1), β endosulfan (2), endosulfan sulphate, endrin, lindane, aldrin, dieldrin, methoxychlor and hexachlorocyclohexanes (alpha; beta; gamma; delta). Except for aldrin, all 16 OCPs targeted in the present study were detected. The OCP residue levels ranged from below detection limit (BDL) to 7.44 ± 0.66 μg/L, BDL to 6.39 ± 1.10 μg/kg ww and BDL to 319.74 ± 66.94 μg/kg ww in water, sediment and fish samples respectively. Some OCP concentrations exhibited significant differences across the sampling sites (p < .05). The residue level of endosulfan was above the European Union standard, whereas the target hazard quotient of heptachlor epoxide was above 1, therefore being unsafe for human consumption. The present study results indicate that most of organochlorine pesticides though banned in Kenya are still detected in the environment, posing potential long‐term health hazards to humans. Accordingly, environmental monitoring programme and mitigation strategies of reducing pollutant inputs into the lake is recommended, as well as an immediate ban on harvesting and consumption of fish from Lake Nakuru.
Framing the change and changing frames: Tensions in participative strategy development
Authors: Zimmermann Angelika , Kenter Jasper O.
Published: January 2023

Participative strategy development serves to integrate the interests and perspectives of multiple stakeholders involved in today's complex environmental challenges, aiming at a better‐informed strategy for tackling these challenges, increased stakeholder ownership, and more democratic decision making. Prior research has observed inherent tensions between the need for participative strategy to be open to stakeholders' input and the need for closure and guidance. We extend this reasoning using a framing perspective. Our evidence from the development of the England Peat Action Plan suggests that tensions can emerge between the necessary ambiguous initial framing of intended change and the persistence of stakeholders' different framings of this change as well as perceptions of lacking knowledge, guidance, and control. We argue that strategy openness can thereby impede stakeholders' willingness and ability to change and counteract the strategy's aim for major transformation. Interactive spaces help mitigate the tensions and facilitate stakeholders' willingness and ability for change.

Related Articles

Brant, Hanna K., Nathan Myers, and Katherine L. Runge. 2017. “Promotion, Protection, and Entrepreneurship: Stakeholder Participation and Policy Change in the 21st Century Cures Initiative.” Politics & Policy 45(3): 372–404. https://doi.org/10.1111/polp.12201.

Bryson, John R., Michael Taylor, and Peter W. Daniels. 2008. “Commercializing ‘Creative’ Expertise: Business and Professional Services and Regional Economic Development in the West Midlands, United Kingdom.” Politics & Policy 36(2): 306–28. https://doi.org/10.1111/j.1747‐1346.2008.00107.x.

Falkenström, Erica, and Stefan Svallfors. 2022. “The Knowledge–Management Complex: From Quality Registries to National Knowledge‐Driven Management in Swedish Health Care Governance.” Politics & Policy 50(5): 1053–66. https://doi.org/10.1111/polp.12497.
Minimal invasiveness in nonsurgical periodontal therapy
Authors: Ribeiro Fernanda V. , Mehta Jaimini J. , Monteiro Mabelle F. , Moore Jatinder , Casati Marcio Z. , Nibali Luigi
Published: January 2023

Periodontal treatment is quickly moving towards a philosophy consisting of a less invasive approach. In this context, minimally invasive nonsurgical therapy (MINST) is a promising option. This paper reviews the concepts behind minimal invasiveness in nonsurgical periodontology and reports the state‐of the art evidence for this topic. Instruments used and protocols suggested for these applications are introduced and discussed. The original papers reviewed show probing pocket depth (PPD) reductions and clinical attachment level (CAL) gains ranging from 2 to 4 mm between baseline and 6 months to 5 years posttreatment for intrabony defects and from 1.5 to 3 mm between baseline and 2‐6 months of follow‐up for full‐mouth results. These clinical outcomes are accompanied by statistically significant reductions in radiographic bone defect depth and increases in intrabony defect angles posttreatment. Wound healing mechanisms following MINST are presented, and clinical applications and directions for future research are suggested.
Demographic Trends
Authors: Azadi Pooya , Mesgaran Mohsen B. , Mirramezani Matin
Published: January 2023

This chapter presents the past trends in Iran’s population dynamics and discusses future projections. It describes the changes in population size and characteristics over the past half century, with a particular focus on patterns of fertility, age composition, marriage, urbanization, and population distribution across provinces. It also argues how demographic trends will continue to play a central role in Iran’s future trajectory of development.
The Agriculture Sector
Authors: Azadi Pooya , Mesgaran Mohsen B. , Mirramezani Matin
Published: January 2023

This chapter is concerned with Iran’s water crisis, which is one of the most consequential issues that the current and future generations of Iranians have to deal with. It begins with explaining historical trends in domestic food supply, focusing on agricultural water consumption, cultivated area, patterns of irrigation, and the amount and composition of agricultural output. It then shows how historical demand for food has been affected by changes in population and the per capita income. The chapter ends with an analysis of future food demand and the increasing need for the import of food warranted by the need to reduce water consumption.
Introduction
Authors: Krohn-Hansen Christian
Published: January 2023

The Dominican Republic has posted impressive economic growth rates over the past twenty-five to thirty years. Despite this, the generation of new, good jobs has been remarkably weak. How have ordinary and poor Dominicans worked and lived in the shadow of the country’s conspicuous growth rates? This book considers this question through an ethnographic exploration of the popular economy in the Dominican capital. Throughout the book’s analyses, Krohn-Hansen is concerned with a broader question: How should researchers tackle the challenges that the phenomena of jobless growth and “no labor” futures raise for anthropology and political-economic analysis? The first two sections sketch the author’s most general research questions, analytical position, and methods.
The End of the Colmado ?
Authors: Krohn-Hansen Christian
Published: January 2023

Until recently, most Dominicans purchased food and groceries in colmados and in public markets. El colmado, the small barrio or street-corner store, continues to be the most widespread small business in the country. Chapter 3 discusses the major changes in the Dominican retail distribution sector over recent decades, and analyzes the present conditions and practices of the capital’s colmados. The chapter argues that, although the economic climate for the colmados in Santo Domingo has become significantly tougher, they will nonetheless remain an important part of the Dominican capital in the years to come, for three reasons. First, the colmado has a proud national history—it has already shown itself to be resilient and flexible. Second, the colmado has been, and continues to be, a key site for the production and experience of lo criollo—what it means to be Dominican. Third, it still fills an economic niche.
For Cooperatives
Authors: Krohn-Hansen Christian
Published: January 2023

Chapter 4 focuses on the country’s cooperative movement. Over the last two decades, Dominican savings and credit cooperatives have become increasingly important. The chapter discusses how these business ventures are organized, and how they function economically and politically. It seeks particularly to show three things. First, the Dominican cooperativa, or cooperative, is a shifting entity—an open, elastic category. Second, Dominican cooperatives are regarded by the members as empresas, or business firms—but firms with a social, more human purpose. Put differently, today’s Dominican cooperative is more an instrumentality of insertion into the interstices of capitalist time as a survival strategy. The glue of the cooperative is the will for shared help. Third, these enterprises represent a certain political—democratic—hope. Most of them seek to train their members in a more inclusive way of running affairs. At their best, cooperatives’ practices challenge the nation’s ingrained, authoritarian political patterns.
The Habsburg Empire and the Bosnian Province
Authors: Ohanyan Anna
Published: January 2023

This chapter starts with a discussion of the neighborhood effect on the political peripheries of the Habsburg empire, focusing largely on the imperial institutions and their colonial governance style on the empire’s political peripheries. It then focuses on the stressors that imperial governance applies to the regional connectivity on the peripheries. As with the subsequent two empirical chapters, this chapter focuses on a single political periphery, in this case the Bosnian province. This chapter is a study of regional connectivity expressed in terms of the existing bridging/bonding social capital and the density of civic institutions. This discussion is then integrated with chapter 7, on the conflict onset and severity of the Bosnian war in the post-Cold War period.
A Novel Data Assimilation-Based Real-Time State Estimation Method for Gas Influx Profiling During Riser Gas Events
Authors: Wei Chen , Tabjula Jagadeeshwar L. , Sharma Jyotsna , Chen Yuanhang
Published: January 2023

Riser gas events during offshore drilling operations are hazardous and challenging to control. Therefore, knowledge of the gas influx sizes and distributions in a marine drilling riser is critical for the selection of riser gas handling methods and the estimation of risks of riser gas unloading. An extended Kalman filter-based data assimilation method is developed and evaluated for the real-time estimation of gas influx rates and void fraction distributions in a riser during riser gas handling. Full-scale experiments were conducted in this study for the evaluation of the proposed data assimilation method. An offshore well, which consists of a marine drilling riser and a wellbore below the subsea blowout preventer, was simulated by a 1572-m-deep experimental well. Real-time measurement data, including surface and downhole pressures, pump rates, and liquid outflow rates, were used to estimate the downhole gas influx rates using the Kalman filter. An online calibrated drift-flux model based on data assimilation is used to estimate the distributions of void fractions in the riser over time. The measurement data from a gas flowmeter and the distributed fiber-optic sensing were used to validate the estimation results, and satisfying performance was seen from the presented method. This study proposed a novel data assimilation-based state estimation method by maximizing the use of measurement data of different types from the available managed pressure drilling systems. This method enables the more accurate estimation and prediction of gas behaviors in a riser and helps to facilitate real-time decision-making during riser gas handling.
Self-Presentation and Black Male College Athletes at Historically White Institutions
Authors: Howe Jonathan E.
Published: January 2023

Black male college athletes (BMCAs) are in a unique position within the contexts of historically white institutions and Division I college athletics. Recently, BMCAs have increasingly presented themselves in ways that highlight specific social identities or even in opposition to the college athletic system and higher education environment. However, little has changed as power and privilege remain central forces in white-dominated settings. This constructivist grounded theory study examines how historically white institution and Division I athletic environments influence self-presentation of BMCAs through a Black critical theory lens. The experiences of 16 BMCAs illuminated how self-presentation was influenced by academic and athletic settings, Division I subdivision characteristics, and sport-specific contexts. I conclude with recommendations and directions for future research.
Cullin-5 deficiency orchestrates the tumor microenvironment to promote mammary tumor development through CREB1-CCL2 signaling
Authors: Chen Si , Shao Fangyuan , Zeng Jianming , Guo Sen , Wang Lijian , Sun Heng , Lei Josh Haipeng , Lyu Xueying , Gao Shuai , Chen Qiang , Miao Kai , Xu Xiaoling , Deng Chu-Xia
Published: January 2023

Breast cancer–associated gene 1 (
Brca1
) deficiency induces the onset of breast cancer formation, accompanied with extensive genetic alterations. Here, we used both the sleeping beauty transposon mutagenesis system and CRISPR-Cas9–mediated genome-wide screening in mice to identify potential genetic alterations that act synergistically with
Brca1
deficiency to promote tumorignesis. Both approaches identified Cullin-5 as a tumor suppressor, whose mutation enabled
Brca1
-deficient cell survival and accelerated tumorigenesis by orchestrating tumor microenvironment. Cullin-5 suppresses cell growth through ubiquitylating and degrading adenosine 3′,5′-monophosphate–responsive element binding protein 1 (CREB1), especially under protein damage condition. Meanwhile, Cullin-5 deficiency activated CREB1-CCL2 signaling and resulted in the accumulation of monocytes and polymorphonuclear myeloid–derived suppressor cells, reduction of T cells that benefit tumor progression in both
Brca1
-deficient cells and wild-type cells. Blocking CREB1 activity either through gene knockout or specific inhibitor treatment suppressed changes in the tumor microenvironment caused by Cullin-5 deficiency and blocked tumor progression.
TEAD4 is a master regulator of high-risk nasopharyngeal carcinoma
Authors: Wang Ya-Qin , Wu Dong-Hong , Wei Denghui , Shen Jia-Yi , Huang Zi-Wei , Liang Xiao-Yu , Cho William C.S. , Ma Jun , Lv Jiawei , Chen Yu-Pei
Published: January 2023

The molecular basis underlying nasopharyngeal carcinoma (NPC) remains unclear. Recent progress in transcriptional regulatory network analysis helps identify the master regulator (MR) proteins that transcriptionally define malignant tumor phenotypes. Here, we investigated transcription factor-target interactions and identified TEA domain transcription factor 4 (TEAD4) as an MR of high-risk NPC. Precisely, TEAD4 promoted NPC migration, invasion and cisplatin resistance, depending on its autopalmitoylation. Mechanistically, YTHDF2 (YTH domain family 2) recognized WTAP (Wilms tumor 1–associating protein)–mediated
TEAD4
m
6
A methylation to facilitate its stability and led to aberrant up-regulation of TEAD4. Up-regulated TEAD4 further drove NPC progression by transcriptionally activating BZW2 (basic leucine zipper and W2 domains 2) to induce the oncogenic AKT pathway. Moreover, the transcriptional activity of TEAD4 was independent of its canonical coactivators YAP/TAZ. Clinically, TEAD4 serves as an independent predictor of unfavorable prognosis and cisplatin response in NPC. Our data revealed the crucial role of TEAD4 in driving tumor malignancy, thus, may provide therapeutic vulnerability in NPC.
A BMP-2–triggered in vivo osteo-organoid for cell therapy
Authors: Dai Kai , Zhang Qinghao , Deng Shunshu , Yu Yuanman , Zhu Fuwei , Zhang Shuang , Pan YuanZhong , Long Dandan , Wang Jing , Liu Changsheng
Published: January 2023

Cell therapies and regenerative medicine interventions require an adequate source of therapeutic cells. Here, we demonstrate that constructing in vivo osteo-organoids by implanting bone morphogenetic protein–2–loaded scaffolds into the internal muscle pocket near the femur of mice supports the growth and subsequent harvest of therapeutically useful cells including hematopoietic stem/progenitor cells (HSPCs), mesenchymal stem cells (MSCs), lymphocytes, and myeloid cells. Profiling of the in vivo osteo-organoid maturation process delineated three stages—fibroproliferation, osteochondral differentiation, and marrow generation—each of which entailed obvious changes in the organoid structure and cell type distribution. The MSCs harvested from the osteochondral differentiation stage mitigated carbon tetrachloride (CCl
4
)–induced chronic liver fibrosis in mice, while HSPCs and immune cells harvested during the marrow generation stage rapidly and effectively reconstituted the impaired peripheral and solid immune organs of irradiated mice. These findings demonstrate the therapeutic potentials of in vivo osteo-organoid–derived cells in cell therapies.
ArpC5 isoforms regulate Arp2/3 complex–dependent protrusion through differential Ena/VASP positioning
Authors: Fäßler Florian , Javoor Manjunath G. , Datler Julia , Döring Hermann , Hofer Florian W. , Dimchev Georgi , Hodirnau Victor-Valentin , Faix Jan , Rottner Klemens , Schur Florian K.M.
Published: January 2023

Regulation of the Arp2/3 complex is required for productive nucleation of branched actin networks. An emerging aspect of regulation is the incorporation of subunit isoforms into the Arp2/3 complex. Specifically, both ArpC5 subunit isoforms, ArpC5 and ArpC5L, have been reported to fine-tune nucleation activity and branch junction stability. We have combined reverse genetics and cellular structural biology to describe how ArpC5 and ArpC5L differentially affect cell migration. Both define the structural stability of ArpC1 in branch junctions and, in turn, by determining protrusion characteristics, affect protein dynamics and actin network ultrastructure. ArpC5 isoforms also affect the positioning of members of the Ena/Vasodilator-stimulated phosphoprotein (VASP) family of actin filament elongators, which mediate ArpC5 isoform–specific effects on the actin assembly level. Our results suggest that ArpC5 and Ena/VASP proteins are part of a signaling pathway enhancing cell migration.
CD47 halts
Ptpn6
-deficient neutrophils from provoking lethal inflammation
Authors: Mazgaeen Lalita , Yorek Matthew , Saini Saurabh , Vogel Peter , Meyerholz David K. , Kanneganti Thirumala-Devi , Gurung Prajwal
Published: January 2023

Mice with SHP1 proteins, which have a single amino acid substitution from tyrosine-208 residue to asparagine (hereafter
Ptpn6
spin
mice), develop an autoinflammatory disease with inflamed footpads. Genetic crosses to study CD47 function in
Ptpn6
spin
mice bred
Ptpn6
spin
×
Cd47
−/−
mice that were not born at the expected Mendelian ratio.
Ptpn6
spin
bone marrow cells, when transferred into lethally irradiated
Cd47
-deficient mice, caused marked weight loss and subsequent death. At a cellular level,
Ptpn6
-deficient neutrophils promoted weight loss and death of the lethally irradiated
Cd47
−/−
recipients. We posited that leakage of gut microbiota promotes morbidity and mortality in
Cd47
−/−
mice receiving
Ptpn6
spin
cells. Colonic cell death and gut leakage were substantially increased in the diseased
Cd47
−/−
mice. Last, IL-1 blockade using anakinra rescued the morbidity and mortality observed in the diseased
Cd47
−/−
mice. These data together demonstrate a protective role for CD47 in tempering pathogenic neutrophils in the
Ptpn6
spin
mice.
Epithelial-intrinsic defects in TGFβR signaling drive local allergic inflammation manifesting as eosinophilic esophagitis
Authors: Laky Karen , Kinard Jessica L. , Li Jenny Min , Moore Ian N. , Lack Justin , Fischer Elizabeth R. , Kabat Juraj , Latanich Rachel , Zachos Nicholas C. , Limkar Ajinkya R. , Weissler Katherine A. , Thompson Robert W. , Wynn Thomas A. , Dietz Harry C. , Guerrerio Anthony L. , Frischmeyer-Guerrerio Pamela A.
Published: January 2023

Allergic diseases are a global health challenge. Individuals harboring loss-of-function variants in transforming growth factor–β receptor (TGFβR) genes have an increased prevalence of allergic disorders, including eosinophilic esophagitis. Allergic diseases typically localize to mucosal barriers, implicating epithelial dysfunction as a cardinal feature of allergic disease. Here, we describe an essential role for TGFβ in the control of tissue-specific immune homeostasis that provides mechanistic insight into these clinical associations. Mice expressing a TGFβR1 loss-of-function variant identified in atopic patients spontaneously develop disease that clinically, immunologically, histologically, and transcriptionally recapitulates eosinophilic esophagitis. In vivo and in vitro, TGFβR1 variant–expressing epithelial cells are hyperproliferative, fail to differentiate properly, and overexpress innate proinflammatory mediators, which persist in the absence of lymphocytes or external allergens. Together, our results support the concept that TGFβ plays a fundamental, nonredundant, epithelial cell–intrinsic role in controlling tissue-specific allergic inflammation that is independent of its role in adaptive immunity.
What variables should inform needle length choice for deltoid intramuscular injection? A systematic review
Authors: Kearns Ciléin , Houghton Claire , Dickinson Emily , Hatter Lee , Bruce Pepa , Krishnamoorthy Srinidhi , Weatherall Mark , Hills Thomas , Doppen Marjan , Ali Mirjalili Seyed , Beasley Richard
Published: January 2023

Objectives

(1) Assess the distribution of skin-to-deltoid-muscle distance (SDMD) at the deltoid intramuscular (IM) injection site; (2) its relationship with demographic and anthropometric variables and (3) Consider the findings in relation to clinical guidance on IM injection, such as COVID-19 vaccines.

Design

Systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Data sources

MEDLINE, EMBASE, ClinicalTrials.gov, Cochrane Library, CINAHL and SCOPUS between June and July 2021 with no publication date limit.

Eligibility criteria

Studies reporting measurements of the SDMD in living adults aged 16 years and older, at the deltoid IM injection site, published in English were considered.

Data extraction and synthesis

Two independent reviewers performed each stage of screening, data extraction and quality assessments using the Joanna Briggs Institute Critical Appraisal Checklist for analytical cross sectional studies.

Results

16 105 papers were identified, of which 11 studies were suitable for review, representing 1414 participants. Heterogeneity in the definition of the deltoid IM injection site, locations measured and methods of measurement precluded meta-analysis. Evidence from ultrasound SDMD measurements demonstrated some patients in all but ‘underweight’ body mass index (BMI) categories, may require needles longer than 25 mm for successful IM injection. Calliper measurements overestimated SDMD compared with ultrasound. Female sex, higher BMI categories and greater weight in women were associated with greater SDMD.

Conclusions

The reviewed evidence was insufficient to inform definitive needle length ‘cut points’ for IM injection based on demographic or anthropomorphic variables. Contemporary clinical guidance currently based on this evidence, including the site of injection and choice of needle length, may result in subcutaneous administration in a small proportion of recipients, particularly if obese or of female sex.

PROSPERO registration number

CRD42021264625.
Reporting of patient involvement: a mixed-methods analysis of current practice in health research publications using a targeted search strategy
Authors: Weschke Sarah , Franzen Delwen Louise , Sierawska Anna Karolina , Bonde Lea-Sophie , Strech Daniel , Schorr Susanne Gabriele
Published: January 2023

Objectives

To evaluate the extent and quality of patient involvement reporting in examples of current practice in health research.

Design

Mixed-methods study. We used a targeted search strategy across three cohorts to identify health research publications that reported patient involvement: original research articles published in 2019 in the British Medical Journal (BMJ), articles listed in the Patient-Centered Outcomes Research Institute (PCORI) database (2019), and articles citing the GRIPP2 (Guidance for Reporting Involvement of Patients and Public) reporting checklist for patient involvement or a critical appraisal guideline for user involvement. Publications were coded according to three coding schemes: ‘phase of involvement’, the GRIPP2-Short Form (GRIPP2-SF) reporting checklist and the critical appraisal guideline.

Outcome measures

The phase of the study in which patients were actively involved. For the BMJ sample, the proportion of publications that reported patient involvement. The quality of reporting based on the GRIPP2-SF reporting guideline. The quality of patient involvement based on the critical appraisal guideline. Quantitative and qualitative results are reported.

Results

We included 86 publications that reported patient involvement. Patients were most frequently involved in study design (90% of publications, n=77), followed by study conduct (71%, n=61) and dissemination (42%, n=36). Reporting of patient involvement was often incomplete, for example, only 40% of publications (n=34) reported the aim of patient involvement. While the methods (57%, n=49) and results (59%, n=51) of involvement were reported more frequently, reporting was often unspecific and the influence of patients’ input remained vague. Therefore, a systematic assessment of the quality and impact of patient involvement according to the critical appraisal guideline was not feasible across samples.

Conclusions

As patient involvement is increasingly seen as an integral part of the research process and requested by funding bodies, it is essential that researchers receive specific guidance on how to report patient involvement activities. Complete reporting builds the foundation for assessing the quality of patient involvement and its impact on research.