bluuebunny/crossref_metadata_2025 huggingface dataset:
Chasing the Numinous: Hungry Ghosts in the Shadow of the Psychedelic Renaissance
Authors: Osterhold Helge Michael , Fernandes‐Osterhold Gisele
Published: August 2023

In recent years a renewed scientific, public and commercial interest in psychedelic medicines can be observed across the globe. As research findings have been generally promising, there is hope for new treatment possibilities for a number of difficult‐to‐treat mental health concerns. While honouring positive developments and therapeutic promise in relation to the medical use of psychedelics, this paper aims to shine a light on some underlying psycho‐cultural shadow dynamics in the unfolding psychedelic renaissance. This paper explores whether and how the multi‐layered collective fascination with psychedelics may yet be another symptom pointing towards a deeper psychological and spiritual malaise in the modern Western psyche as diagnosed by C. G. Jung. The question is posed whether the West’s feverish pursuit of psychedelic medicines—from individual consumption to entheogenic tourism, from capitalist commodification of medicines and treatments to the increasing number of ethical scandals and abuse through clinicians and self‐proclaimed shamans—is related to a Western cultural complex. As part of the discussion, the archetypal image of the Hungry Ghost, known across Asian cultural and religious traditions, is explored to better understand the aforementioned shadow phenomena and point towards mitigating possibilities.
Traceability in the Indian dairy industry: Concept and practice
Authors: Malik Mohit , Malik Aanchal , Gahlawat Vijay Kumar , Mor Rahul S
Published: August 2023

The rise in milk adulteration and contamination, fraud incidents and improper handling necessitates effective traceability systems in the Indian dairy industry. Thus, this review investigates current trends, associated challenges, traceability and its fundamental applications to address food safety and quality issues. The paper covers the evolution of milk adulteration and contamination detection techniques from conventional to emerging. Such information and analytical technologies can improve transparency and safety in the dairy industry by implementing effective traceability systems. This review will explore the challenges and future opportunities associated with the current situation in the Indian dairy industry.
Taxonomy, distribution, and contemporary exposure of terrestrial mammals to floods and human pressure across different areas for biodiversity conservation in China
Authors: SHARNUUD Roman , AMECA Eric I.
Published: August 2023

A significant research focus is placed on identifying animal species and areas at future risk to human‐induced alterations of the environment and long‐term changes in climatic conditions. Yet, the extent to which exposure to extreme climatic events and intense human pressure can increase the risk of harmful impacts on species remains poorly investigated. Focusing on terrestrial mammals in China, one of the world's megadiverse countries, we investigated patterns of contemporary exposure to floods and human pressures and determined their taxonomic representation and distribution across three major area‐based conservation schemes, namely, national nature reserves (NNRs), priority areas for biodiversity conservation (PABCs), and key biodiversity areas (KBAs). Among the 440 species assessed with moderate or high exposure to floods, 327 (∼75%) also qualified as moderate or high in exposure to intense human pressure. These species mainly belong to the orders Chiroptera, Eulipotyphla, and Rodentia. Likewise, there were 305, 311, and 311 species with moderate or high exposure to flood and intense human pressure represented across NNRs, PABCs, and KBAs, respectively. Our findings support the prioritization of KBAs for expansion of site‐based protection efforts such as NNRs in China, considering threats to species from exposure to adverse effects from both extreme climate and human pressure.
Seasonal variation and host sex affect bat–bat fly interaction networks in the Amazonian savannahs
Authors: MEJIA Paulo , URBIETA Gustavo Lima , XAVIER Bruna da Silva , CASTRO Isaí Jorge de , DE TOLEDO José Júlio , GRACIOLLI Gustavo , VIANA DIAS Lucio André , CARVALHO William Douglas
Published: August 2023

Bats are the second‐most diverse group of mammals in the world, and bat flies are their main parasites. However, significant knowledge gaps remain regarding these antagonistic interactions, especially since diverse factors such as seasonality and host sex can affect their network structures. Here, we explore the influence of such factors by comparing species richness and composition of bat flies on host bats, as well as specialization and modularity of bat–bat fly interaction networks between seasons and adult host sexes. We captured bats and collected their ectoparasitic flies at 10 sampling sites in the savannahs of Amapá State, northeastern region of the Brazilian Amazon. Despite female bats being more parasitized and recording greater bat fly species richness in the wet season, neither relationship was statistically significant. The pooled network could be divided into 15 compartments with 54 links, and all subnetworks comprised >12 compartments. The total number of links ranged from 27 to 48 (for the dry and wet seasons, respectively), and female and male subnetworks had 44 and 41 links, respectively. Connectance values were very low for the pooled network and for all subnetworks. Our results revealed higher bat fly species richness and abundance in the wet season, whereas specialization and modularity were higher in the dry season. Moreover, the subnetwork for female bats displayed higher specialization and modularity than the male subnetwork. Therefore, both seasonality and host sex contribute in different ways to bat–bat fly network structure. Future studies should consider these factors when evaluating bat–bat fly interaction networks.
Portugal: Political Developments and Data in 2022
Authors: MAGONE JOSÉ M.
Published: August 2023

In this article, the main events of political life in Portugal are discussed. It includes a report on general elections in 2022, the formation of a new Socialist absolute majority government led by Prime Minister Antonio Costa, and major parliamentary decisions and debates. The year 2022 started with early general elections, strengthening the ruling Socialist Party, which won a majority of seats in the national Parliament. However, it took some time for the new government to learn to govern in the new context.
Evaluation of treatment and restoration preferences in deep carious teeth with various pulp exposure sizes: A questionnaire‐based survey
Authors: Yurdagüven Gülşah Yenier , Işık Vasfiye , Çiftçioğlu Elif , Ulukapı Haşmet , Kayahan Mehmet Baybora
Published: August 2023

This study evaluated the management preferences in a deep carious vital tooth. A questionnaire was e‐mailed to members of the Turkish Dental Association. The questionnaire included a photograph and radiographs of an extremely deep carious molar (#16) of a 30‐year‐old man suffering from cold and chewing sensitivity. The dentists were asked to choose treatments for pulp exposure of <1, 1–2, and ≥2 mm and a permanent restoration. Chi‐squared test was used to analyse data (p < 0.05). 504 (4.84%) of 10 411 dentists responded. When the pulp exposure was <1 mm: direct pulp capping (84.9%); 1–2 mm: root canal treatment (49.6%); ≥2 mm: root canal treatment (85.7%) were the most preferred treatments. 69.6% of the respondents chose direct composite restorations. If the tooth would be an abutment, most respondents preferred root canal treatment, regardless of the perforation size. The extent of pulp exposure and the type of permanent restoration influenced the treatment decision‐making process.
Feasibility and preliminary efficacy of a community support intervention for people with opioid use disorder
Authors: Kidorf Michael , Peirce Jessica , Brooner Robert K. , Yan Haijuan , Latkin Carl
Published: August 2023

Background and Objectives

People receiving agonist treatment for opioid use disorder often have family or friends who do not use illicit substances and could be mobilized to support recovery efforts. The present study evaluates the feasibility and preliminary efficacy of a community support intervention (CSI) designed to increase drug‐free social support and expand drug‐free network support.

Methods

Participants receiving methadone treatment and using illicit drugs (n = 33) were randomly assigned to a weekly CSI or education group for 12 weeks. CSI participants attended the group with a drug‐free family member or friend, and were scheduled to engage together in two community activities per week designed to meet drug‐free people. Education participants attended a weekly education group and were given two weekly written homework sessions.

Results

CSI groups were well attended. CSI participation was associated with reduced conflict with the family member or friend, and with increased engagement in self‐help groups. No condition differences were observed in social network variables or urinalysis results, though four CSI participants (24%) compared to 0 education participants met criteria for substantial (>75%) reductions in drug use. Many eligible patients chose not to participate.

Discussion and Conclusions

These findings suggest good implementation feasibility and acceptability, and low demand feasibility. Broader clinical implementation requires strategies to improve patient willingness to enlist available social support.

Scientific Significance

Mobilizing family and friends to provide social support for people engaged in active drug use is possible. More work is needed on how to leverage support to change existing networks.
NATO/US false‐flag attacks in Europe
Authors: Griffin David Ray , Cobb Clifford W.
Published: August 2023

False flag operations are acts of deception carried out by government officials to blame other countries or political groups for an attack against the nation with the aim of stirring up a desire for retribution against the supposed perpetrator. Since the effectiveness of a false‐flag operation depends on preventing the truth from becoming widely known, it is impossible to know how often such operations have been carried out. Nevertheless, some historical events have been revealed in time, so we can better understand how they operate. The focus here is on false‐flag operations in Western Europe and Turkey, carried out as part of the Gladio program during the Cold War under the supervision of the CIA. In each case, the CIA persuaded NATO members to recruit right‐wing operatives to engage in terrorist actions and then blame the resulting deaths on left‐wing groups, mostly communists. In this way, the United States used deception and terror to prevent communists from gaining power in Europe after World War II.
Does Differentiated Key Audit Matter in Unqualified Audit Reports Indicate Increased Financial Misstatement Risk? Evidence from China*
Authors: Ma Qianqun , Zhou Jianan , Wang Kongwen , Wang Qi
Published: August 2023

This study examines whether differentiated disclosure of key audit matter (KAM) in China indicates a higher financial misstatement risk. Our empirical study demonstrates that financial statements with less boilerplate KAM are more likely to be subsequently restated than those with more boilerplate KAM. This association is only pronounced for smaller auditing firms in stronger legal environments. Additionally, auditors who report differentiated KAM are likely to disclose more risk‐related information. Moreover, clients are more likely to restate financial reports when the KAM relates to managers' subjective estimations.
Time‐restricted eating for chronodisruption‐related chronic diseases
Authors: Cheng Wai‐Yin , Desmet Louis , Depoortere Inge
Published: August 2023

The circadian timing system enables organisms to adapt their physiology and behavior to the cyclic environmental changes including light–dark cycle or food availability. Misalignment between the endogenous circadian rhythms and external cues is known as chronodisruption and is closely associated with the development of metabolic and gastrointestinal disorders, cardiovascular diseases, and cancer. Time‐restricted eating (TRE, in human) is an emerging dietary approach for weight management. Recent studies have shown that TRE or time‐restricted feeding (TRF, when referring to animals) has several beneficial health effects, which, however, are not limited to weight management. This review summarizes the effects of TRE/TRF on regulating energy metabolism, gut microbiota and homeostasis, development of cardiovascular diseases and cancer. Furthermore, we will address the role of circadian clocks in TRE/TRF and propose ways to optimize TRE as a dietary strategy to obtain maximal health benefits.
Unintended impact of pharmacovigilance regulatory interventions: A systematic review
Authors: Lasys Tomas , Santa‐Ana‐Tellez Yared , Siiskonen Satu J. , Groenwold Rolf H. H. , Gardarsdottir Helga
Published: August 2023

Aims

Studies assessing the impact of pharmacovigilance regulatory interventions often focus on the expected (or intended) outcomes, while any possible unintended impact may be overlooked. The update of the Good Pharmacovigilance Practice guideline in 2017 elaborated on impact assessment, emphasizing the need also to assess possible unintended impact. This systematic literature review investigated how often the unintended impact of regulatory interventions was considered in publications of studies investigating pharmacovigilance regulatory interventions in Europe.

Methods

We conducted a systematic review of the literature on MEDLINE and EMBASE from 1 January 2012 to 28 February 2022 to identify publications that investigated the impact of regulatory interventions in Europe. The primary outcome of the study was the number of publications reporting assessments of unintended impact. In addition, we studied the characteristics of these publications, including the type of outcomes assessed, the analytical methods applied and the type of data used.

Results

In total, 96 publications were included in the analysis. The unintended impact of pharmacovigilance regulatory interventions was investigated in 23 of 96 publications (24%). The drug classes most frequently studied in the publications assessing unintended impact of regulatory interventions were oral glucose‐lowering drugs (n = 6, 26%), opioids (n = 4, 17%), antidepressants (n = 4, 17%) and antipsychotics (n = 3, 13%). The reported methods to assess the unintended impact were interrupted time series (n = 10, 43%) and descriptive statistics with or without significance testing (n = 2 [9%] and n = 9 [39%], respectively). The outcomes selected for unintended impact assessments included the use of other drugs (n = 16, 70%), health outcomes (n = 8, 35%) and behavioural changes (n = 4, 17%). Most of the publications reported on the use of electronic health record databases (n = 13, 57%) or claims databases (n = 13, 57%), while registries were used in 4 publications (17%).

Conclusion

The unintended impact of pharmacovigilance regulatory interventions was reported in only a quarter of identified publications. There was no apparent increase in attention to unintended impact assessments after the update of the Good Pharmacovigilance Practice guidelines.
Bio‐evaluation of poly(lactic‐co‐glycolic) acid nanoparticles loaded with radiolabelled rifampicin
Authors: Rather Imran , Shafiq Nusrat , Shukla Jaya , Kaur Gurvinder , Pandey Somit , Bhandari Ritika Kondel , Pandey Avaneesh Kumar , Mittal B. R. , Khuller G. K. , Sharma Navneet , Malhotra Samir
Published: August 2023

Aims

The poly(lactic‐co‐glycolic) acid (PLGA) nanoparticles of tubercular drugs have been demonstrated to have a sustained release profile over 7 days. There is no information on the location or mode of release of these nanoparticles in living systems. Therefore, we have planned the study to explore the pharmacokinetics and biodistribution of PLGA rifampicin nanoparticles in healthy human volunteers. We aim to study the distribution pattern of PLGA‐loaded nano‐formulation of radiolabelled rifampicin in humans.

Methods

Rifampicin was labelled with 99mTc by indirect method and nanoparticles were prepared by a single emulsion evaporation method. To investigate the pharmacokinetics and biodistribution of nanoparticles, a single dose of 450 mg of rifampicin was administered orally to healthy human volunteers divided into two different groups.

Results

Following a single oral dosage of the rifampicin nanoformulation, the pharmacokinetic (PK) parameters were significantly different between the nanoparticle and conventional groups: area under the concentration–time curve (AUC = 113.8 vs. 58.6; P < .001), mean residence time (MRT = 16.2 vs. 5.8; P < .01) and elimination rate constant (Ke = 0.04 vs. 0.10; P < .05). Also, Single‐photon emission computed tomography/computed tomography (SPECT/CT) images revealed biodistribution of nanoparticles in the distal portions of the intestine, which is consistent with our dosimetry analysis.

Conclusions

Significant difference in PK parameters and biodistribution of nanoparticles in spleen and lymph nodes with maximum deposition were observed in the large intestine. The nanoparticle distribution pattern may be advantageous for the treatment of intestinal or lymph node tuberculosis (TB) and has the potential to result in a lower dose of rifampicin nanoformulation for the treatment of pulmonary TB.
Pre‐transplant and longitudinal changes in faecal microbiome characteristics are associated with subsequent development of chronic graft‐versus‐host disease
Authors: El Jurdi Najla , Holtan Shernan G. , Hoeschen Andrea , Velguth Jessica , Hillmann Benjamin , Betts Brian C. , MacMillan Margaret L. , Weisdorf Daniel J. , Khoruts Alexander , Rashidi Armin , Shields‐Cutler Robin
Published: August 2023

The role of the gastrointestinal microbiome in predisposing to chronic graft‐versus‐host disease (cGVHD), an immune‐mediated haematopoietic cell transplant (HCT) complication, is not well defined. We examined the relationship of the host faecal microbiome with subsequent cGVHD development by analysing baseline stool samples as well as post‐HCT changes in microbiome composition and metabolite pathway analyses. We analysed pre‐transplant baseline samples from 11 patients who subsequently developed cGVHD compared to 13 controls who did not develop acute GVHD or cGVHD at any time. We found a significant differential abundance of multiple taxa at baseline between cGVHD versus controls, including the Actinobacteria phylum and Clostridium genus. A subgroup analysis of longitudinal samples within each patient revealed a greater loss of alpha diversity from baseline to post‐engraftment in patients who subsequently developed cGVHD. Metabolic pathways analysis revealed that two pathways associated with short‐chain fatty acid metabolism were enriched in cGVHD patient microbiomes: β‐oxidation and acyl‐CoA synthesis, and γ‐aminobutyrate shunt. In contrast, a tryptophan catabolism pathway was enriched in controls. Our findings show a distinct pattern of baseline microbiome and metabolic capacity that may play a role in modulating alloreactivity in patients developing cGVHD. These findings support the therapeutic potential of microbiome manipulation for cGVHD prevention.
A Group Psychoanalytic Approach to the Social Dreaming Matrix: A Found‐and‐Created Device
Authors: Salaam Abdel‐Malek Hana
Published: August 2023

To differentiate the Social Dreaming Matrix from Group Relations Conferences, Gordon Lawrence provided a specific denomination, framework and primary task. Despite these new parameters, Lawrence understood that group dynamics persisted in the Matrix, perceiving social dreaming and group dynamics as two lenses of a binocular informing the Matrix. However, to fulfil the Matrix's primary task of accessing the social unconscious, he advocated a non‐psychoanalytic monocular vision emphasizing social dreaming. In this article, I argue that the Social Dreaming Matrix and the Dream Reflection Dialogue that follows are, from a psychoanalytic perspective, two moments of a group whose primary task is Social Dreaming. Looking from a psychoanalytic perspective through the two lenses of social dreaming and group dynamics provides a wider perspective of the social unconscious, generating insights. This group psychoanalytic approach is a found‐and‐created framework rediscovering and recreating the object‐Social Dreaming Matrix framework proposed by Lawrence. To support this argument, I analysed a series of Social Dreaming Matrixes and Dream Reflection Dialogues occurring during a social dreaming training programme to show how the unfolding group dynamics revealed the social unconscious as did social dreaming.
Measuring Economic Integration in Developing Countries: The Case of Central America
Authors: Recinos Nelson Joaquin Salazar , del Pozo Pedro Caldentey , Delgado M. Carmen
Published: August 2023

This article builds a composite index, the Central American Integration Index (IIC‐AMPI), to measure economic integration. This index utilises a robust methodology and conceptual framework. The study shows that IIC‐AMPI is responsive to variable changes and resistant to outliers. The findings indicate that the Deep Integration Process initiative dominates the current integration trend, as seen in the regional average score from 2015 to 2017, aligning with Guatemala and Honduras. Nicaragua demonstrates the most consistent progress, while Panama lags behind. The evidence supports the Customs Union as Central America's future integration path, highlighting the index's ability to capture the dynamic reality of economic integration.
Space‐for‐time substitutions in climate change ecology and evolution
Authors: Lovell Rebecca S. L. , Collins Sinead , Martin Simon H. , Pigot Alex L. , Phillimore Albert B.
Published: August 2023

In an epoch of rapid environmental change, understanding and predicting how biodiversity will respond to a changing climate is an urgent challenge. Since we seldom have sufficient long‐term biological data to use the past to anticipate the future, spatial climate–biotic relationships are often used as a proxy for predicting biotic responses to climate change over time. These ‘space‐for‐time substitutions’ (SFTS) have become near ubiquitous in global change biology, but with different subfields largely developing methods in isolation. We review how climate‐focussed SFTS are used in four subfields of ecology and evolution, each focussed on a different type of biotic variable – population phenotypes, population genotypes, species' distributions, and ecological communities. We then examine the similarities and differences between subfields in terms of methods, limitations and opportunities. While SFTS are used for a wide range of applications, two main approaches are applied across the four subfields: spatial in situ gradient methods and transplant experiments. We find that SFTS methods share common limitations relating to (i) the causality of identified spatial climate–biotic relationships and (ii) the transferability of these relationships, i.e. whether climate–biotic relationships observed over space are equivalent to those occurring over time. Moreover, despite widespread application of SFTS in climate change research, key assumptions remain largely untested. We highlight opportunities to enhance the robustness of SFTS by addressing key assumptions and limitations, with a particular emphasis on where approaches could be shared between the four subfields.
Abnormalities in Clostridioides and related metabolites before ACTH treatment may be associated with its efficacy in patients with infantile epileptic spasm syndrome
Authors: Wan Lin , Shi Xiuyu , Yan Huimin , Liang Yan , Liu Xinting , Zhu Gang , Zhang Jing , Wang Jing , Wang Mingbang , Yang Guang
Published: August 2023

Objective

Adrenocorticotropic hormone (ACTH) is the first‐line treatment of infantile epileptic spasm syndrome (IESS). Its reported effectiveness varies, and our current understanding regarding the role of gut microbiota composition in IESS treatment response is limited. This study assessed the microbiome–metabolome association to understand the role and mechanism of gut microbiota composition in IESS treatment outcomes.

Methods

Children with IESS undergoing ACTH treatment were enrolled. Pre‐treatment stool and serum samples were collected for 16S rRNA gene sequencing and liquid chromatography–tandem mass spectrometry, respectively. The children were divided into “responsive” and “non‐responsive” groups, and gut microbiota and serum metabolome differences were analyzed.

Results

Of the 30 patients with IESS, 14 responded to ACTH and 16 did not. The “non‐responsive” group had larger maleficent Clostridioides and Peptoclostridium_phage_p630P populations (linear discriminant analysis >2; false discovery rate q < 0.05). Ten metabolites were upregulated (e.g., xanthurenic acid) and 15 were downregulated (e.g., vanillylmandelic acid) (p < 0.05). Association analysis of the gut microbiome and serum metabolome revealed that Clostridioides and Peptoclostridium_phage_p630P2 were positively correlated with linoleic and xanthurenic acids, while Clostridioides was negatively correlated with vanillylmandelic acid (p < 0.05). A classifier using differential gut bacteria and metabolites achieved an area under the receiver operating characteristic curve of 0.906 to distinguish responders from non‐responders.

Conclusion

This study found significant differences in pre‐treatment gut microbiota and serum metabolome between children with IESS who responded to ACTH and those who did not. Additional exploration may provide valuable information for treatment selection and potential interventions. Our results suggest that varying ACTH responses in patients with IESS may be associated with increased gut Clostridioides bacteria and kynurenine pathway alteration, but additional experiments are needed to verify this association.
Prothrombin consumption as an indicator of hemorrhagic phenotype in mild platelet function disorders
Authors: Babuty Antoine , Debord Camille , Drillaud Nicolas , Eveillard Marion , Trossaert Marc , Ternisien Catherine , Sigaud Marianne , Cador Emmanuelle , Béné Marie C. , Fouassier Marc
Published: August 2023

Background

The bleeding risk of patients with mild platelet function disorders is difficult to assess and their phenotype remains ill‐explored.

Aim

This study was designed to establish a comprehensive biological phenotype of patients with mild platelet function disorders.

Methods

Twenty patients were included with persistent abnormal light transmission aggregometry (LTA). The ISTH bleeding assessment tool (ISTH‐BAT) was assessed to identify laboratory analyses associated with an abnormal hemorrhagic score.

Results

The majority of patients had defects that might affect Gαi protein signaling pathways or minor abnormalities. No LTA nor flow cytometry parameters were associated with an above‐normal hemorrhagic score. However, prothrombin consumption, which corresponds to the ratio of serum residual factor II to plasma residual factor II, was significantly higher (p = .006) in the abnormal ISTH‐BAT group (mean = 14%, SD = 6) compared with the normal ISTH‐BAT group (mean = 8%, SD 4). Prothrombin consumption was significantly associated with ISTH‐BAT score (r = .5287, IC 95% 0.0986–0.7924, p = .0165).

Conclusion

In this group of patients, there was an association between a pathological bleeding score and increased prothrombin consumption. This test could be used as an additional indicator of platelet function abnormality liable to be related to bleeding risk.
Classification of single‐cell cervical pap smear images using EfficientNet
Authors: Rastogi Priyanka , Khanna Kavita , Singh Vijendra
Published: August 2023

Cervical cancer is the second leading cause of death in women in developing nations like India. The automated cervical cancer screening systems play a critical role in diagnosing the ailment at an early stage. They can also assist in routine cervical cancer screening and decision‐making processes. The underlying binary classifier for detecting cancerous cells is necessary for building computerized screening systems. Thus, this work aims to develop a robust binary classifier capable of classifying single cervical cells as normal and cancerous. The current work aims to improvise the EfficientNet‐B7 with empirical resolution parameters and skilful consolidation of the outcomes of the inner layers using the global pooling layer to improve the binary classification result. The proposed model is trained and evaluated on three independent pap smear datasets. The class activation heatmap visualizes the classification model for better interpretability. The performance of the autonomous classification tasks indicates that the deep learning‐based binary classifier is robust in classifying cancerous cells as it achieves accuracy of 94% on Herlev Dataset which is 2% higher than the other state‐of‐the‐art methods and comparable accuracy of nearly 99% on other cervical cell datasets using the proposed methodology.
Evaluation of the anti‐inflammatory effect of 1,4‐dihydropyridine derivatives
Authors: Facchin Bruno Matheus , Lubschinski Tainá Larissa , Moon Yeo Jim Kinoshita , de Oliveira Paula Giarola Fragoso , Beck Bianca Klafke , da Silva Buss Ziliani , Pollo Luiz Antonio Escorteganha , Biavatti Maique Weber , Sandjo Louis Pergaud , Dalmarco Eduardo Monguilhott
Published: August 2023

Introduction

Inflammation is a physiological event that protects the organism against different factors that lead to loss of tissue homeostasis. Dihydropyridine (DHP) derivatives are heterocyclic compounds known for their different biological activities, including anti‐inflammatory activities.

Objective

To evaluate the anti‐inflammatory activity of 1,4‐dihydropyridine (1,4‐DHP) derivatives using anti‐inflammatory models in vitro, in RAW264.7 cells induced by lipopolysaccharide (LPS) and in vivo using the acute lung injury (ALI) model in mice.

Results

Fifteen compounds derived from 1,4‐DHP were tested in RAW264.7 cells for their cytotoxic effect and cell viability. Thereafter, only the six compounds that showed the highest cell viability were tested for the production or inhibition of the pro‐inflammatory cytokine interleukin 6 (IL‐6). The best compound (compound 4) was tested for its anti‐inflammatory effects in vitro and in vivo, showing inhibition of nitric oxide (NO), pro‐inflammatory cytokines, increased phagocytic activity, and an increase in IL‐10 in vitro. In in vivo tests, compound 4 also reduces the levels of NO, myeloperoxidase (MPO) activity, leukocyte migration, and exudation, as well as reducing the levels of tumor necrosis factor‐alpha (TNF‐α) and IL‐6 and preventing the loss in the lung architecture.

Conclusion

This compound showed important anti‐inflammatory activity, with a significant ability to reduce the production of pro‐inflammatory mediators and increase the phagocytic activity of macrophages and anti‐inflammatory mediator secretion (IL‐10). These findings led us to hypothesize that this compound can repolarize the macrophage response to an anti‐inflammatory profile (M2). Moreover, it was also able to maintain its anti‐inflammatory activity in vivo experiments.
Hepatocyte reprogramming in liver regeneration: Biological mechanisms and applications
Authors: Jiang Mengmeng , Ren Jie , Belmonte Juan Carlos Izpisua , Liu Guang‐Hui
Published: August 2023

The liver is one of the few organs that retain the capability to regenerate in adult mammals. This regeneration process is mainly facilitated by the dynamic behavior of hepatocytes, which are the major functional constituents in the liver. In response to liver injury, hepatocytes undergo remarkable alterations, such as reprogramming, wherein they lose their original identity and acquire properties from other cells. This phenomenon of hepatocyte reprogramming, coupled with hepatocyte expansion, plays a central role in liver regeneration, and its underlying mechanisms are complex and multifaceted. Understanding the fate of reprogrammed hepatocytes and the mechanisms of their conversion has significant implications for the development of innovative therapeutics for liver diseases. Herein, we review the plasticity of hepatocytes in response to various forms of liver injury, with a focus on injury‐induced hepatocyte reprogramming. We provide a comprehensive summary of current knowledge on the molecular and cellular mechanisms governing hepatocyte reprogramming, specifically in the context of liver regeneration, providing insight into potential applications of this process in the treatment of liver disorders, including chronic liver diseases and liver cancer.
Hijacking homeostasis: Regulation of the tumor microenvironment by apoptosis
Authors: Gregory Christopher D.
Published: August 2023

Cancers are genetically driven, rogue tissues which generate dysfunctional, obdurate organs by hijacking normal, homeostatic programs. Apoptosis is an evolutionarily conserved regulated cell death program and a profoundly important homeostatic mechanism that is common (alongside tumor cell proliferation) in actively growing cancers, as well as in tumors responding to cytotoxic anti‐cancer therapies. Although well known for its cell‐autonomous tumor‐suppressive qualities, apoptosis harbors pro‐oncogenic properties which are deployed through non‐cell‐autonomous mechanisms and which generally remain poorly defined. Here, the roles of apoptosis in tumor biology are reviewed, with particular focus on the secreted and fragmentation products of apoptotic tumor cells and their effects on tumor‐associated macrophages, key supportive cells in the aberrant homeostasis of the tumor microenvironment. Historical aspects of cell loss in tumor growth kinetics are considered and the impact (and potential impact) on tumor growth of apoptotic‐cell clearance (efferocytosis) as well as released soluble and extracellular vesicle‐associated factors are discussed from the perspectives of inflammation, tissue repair, and regeneration programs. An “apoptosis‐centric” view is proposed in which dying tumor cells provide an important platform for intricate intercellular communication networks in growing cancers. The perspective has implications for future research and for improving cancer diagnosis and therapy.
Pathways and processes to the embodiment of historical trauma secondary to settler colonialism
Authors: Thomas Nicole A. , Owen Brenda , Ersig Anne L. , Bratzke Lisa C.
Published: August 2023

Aim(s)

This discursive article aims to examine how systemic factors of settler colonialism influence health outcomes among Indigenous peoples in the United States through pathways and processes that may lead to the embodiment of historical trauma.

Design

Discursive paper.

Methods

We completed a comprehensive search of empirical and grey literature between September 2022 and January 2023 in PubMed, CINAHL and Google Scholar. Using these articles as a foundation, we explored factors related to the pathways and processes leading to the embodiment of historical trauma rooted in settler colonialism.

Results

A conceptual framework of the pathways and processes of the embodiment of historical trauma secondary to settler colonialism was developed, and is presented.

Conclusion

The societal and historical context for Indigenous peoples includes harmful settler colonial structures and ideologies, resulting in stressors and historical trauma that impact health outcomes and disparities through the phenomenon of the process of embodiment.

Implications for Nursing

To provide holistic nursing care, nurses must be aware of settler colonialism as a determinant of health. They must be attuned to the pathways and processes through which settler colonial exposures may impact health among Indigenous peoples. Nurses must challenge existing structural inequities to advance health equity and social justice.
When Is Work Unjust? Confronting the Choice between ‘Pluralistic’ and ‘Unifying’ Approaches
Authors: Goff Sarah C.
Published: August 2023

Individuals have different experiences of work when they are self‐employed, when they perform tasks in the gig economy, and when they follow directives from managers. But such differences are not represented in some of the most prominent non‐ideal theories of work. These describe workers as a coherent group, with a position in the structure of the liberal capitalist economy. I present an alternative that does better at acknowledging difference, through a description of work and workers that has greater ‘pluralism’ and less ‘unifying coherence’. Some might insist that their ‘unifying’ description has superior empirical plausibility. But if ‘pluralistic’ descriptions are valid rivals to provide an accurate characterization of our current condition, then we should consider whether their use in theory can serve valuable aims. I identify the distinctive and valuable non‐ideal aims – epistemic, evaluative, and normative – that can be pursued with ‘pluralistic’ descriptions of work and workers.
Form function of sulcus acusticus of the sagittal otolith in seven Sciaenidae (Acanthuriformes) species using geometric morphometrics (southwestern Atlantic)
Authors: Verocai José E. , Cabrera Fernanda , Lombarte Antoni , Norbis Walter
Published: August 2023

The morphology of otoliths determines the function they perform, and it is influenced by genetic and environmental factors. Knowing those relationships is necessary to understand the role of hearing in fish. The objectives of this work were: exploring the shape of the sulcus of the sagittal otolith in seven species of Sciaenidae, in relation to sound production, and analyzing whether the shape and size of the sulcus can be used as a phylogenetic character. For this purpose, geometric morphometry analysis was carried out using landmarks data. It was found that there is an influence of size on the shape of the sulcus, and significant differences were found between the shapes of the sulcus (permutational multivariate analysis of variance). Three general shapes of the sulcus were identified (using principal component analysis, canonical variate analysis, and clustering): (1) in species that produce sounds at dominant frequencies <350 Hz, the deformation of the sulcus showed a tendency towards circularity of the ostium; (2) in those species that produce sounds at frequencies >350 Hz, the ostium showed a flattened ovoid shape, and the cauda increased its length; (3) the species that do not produce sounds, did not show any modifications, relative to the form of consensus. Despite finding sister species that presented similar sulcus shapes in the phylogeny, the results did not confirm that this can be used as a phylogenetic character. This work discusses whether the combined effects of phylogenetic legacy and natural functional selection have led to convergent evolution for the sulcus form. The differences presented by the sulcus of species that occupy the same clade, could indicate that there is a displacement of characters. The sagittal otolith and the sensory macula associated with the sulcus acusticus are highly plastic structures that are subject to strong evolutionary pressure in relation to environmental and behavioral factors, resulting in great variability in shapes that can be associated with a specific character. The variation in the shape of the sulcus would allow the analysed species to coexist in the same coastal soundscapes, without losing their particular hearing needs, even in case of overlapping their spatial and temporal distribution areas.
Voicing singlish from the “middle”: Indexical hybridities of class, race, language, and Singaporeanness
Authors: Khoo Velda
Published: August 2023

The long‐governing People's Action Party in Singapore, cautious of the appeal of Marxist‐type class analyses, recognizes political mileage in promoting the myth of a homogenous “class blind” society. Popular uptakes of this perspective are seen online in parodic uses of new terms high SES and low SES to counter the suggestion that socioeconomic status (SES) is a relevant distinction in Singapore. Such parodies are nevertheless deeply classed, as middle‐class subjectivity emerges through the negation of class‐based extremes (Hall, 2021). This article argues that Singlish has become a powerful instrument for sustaining middle‐class normativity. Its positioning by invested listening subjects (Inoue, 2006) as a hybrid language that equally encompasses speakers of diverse linguistic backgrounds obscures not just class relations but also the central linkage that lies at the heart of a raciolinguistic perspective (Rosa and Flores, 2017). Once class and race are co‐naturalized in this way, speakers can use Singlish to perform an “authentic Singaporeanness,” but this performance is in turn facilitated by a metapragmatic narrative that motivates which forms become enregistered as Singlish.
Consensus, controversy, and chaos in the attribution of characteristics to the morally exceptional
Authors: Fleeson William , Furr R. Michael , Jayawickreme Eranda , Luke Dillon , Prentice Mike , Reynolds Caleb J. , Parham Ashley Hawkins
Published: August 2023

Objective

What do people see as distinguishing the morally exceptional from others? To handle the problem that people may disagree about who qualifies as morally exceptional, we asked subjects to select and rate their own examples of morally exceptional, morally average, and immoral people.

Method

Subjects rated each selected exemplar on several enablers of moral action and several directions of moral action. By applying the logic underlying stimulus sampling in experimental design, we evaluated perceivers’ level of agreement about the characteristics of the morally exceptional, even though perceivers rated different targets.

Results

Across three studies, there was strong subjective consensus on who is morally exceptional: those who are empathetic and prone to guilt, those who reflect on moral issues and identify with morality, those who have self‐control and actually enact moral behaviors, and those who care about harm, compassion, fairness, and honesty. Deep controversies also existed about the moral directions pursued by those seen as morally exceptional: People evaluated those who pursued similar values and made similar decisions more favorably.

Conclusion

Strong consensus suggests characteristics that may push a person to go beyond normal expectations, that the study of moral exceptionality is not overly hindered by disagreement over who is morally exceptional, and that there is some common ground between disagreeing camps.
Learning technology in health professions education: Realising an (un)imagined future
Authors: Grainger Rebecca , Liu Qian , Gladman Tehmina
Published: August 2023

Context

Technology is being introduced, used and studied in almost all areas of health professions education (HPE), often with a claim of making HPE better in one way or another. However, it remains unclear if technology has driven real change in HPE. In this article, we seek to develop an understanding of the transformative capacity of learning technology in HPE.

Methods and Outcomes

We first consider the wider scholarship highlighting the intersection between technology and pedagogy, articulating what is meant by transformation and the role of learning technology in driving educational transformation. We then undertake a synthesis of the current high visibility HPE‐focused research. We sampled the literature in two ways—for the five highest impact factor health professional education journals over the past decade and for all PubMed indexed journals for the last 3 years—and categorised the extant research against the Substitution, Augmentation, Modification, Redefinition model. We found that the majority of research we sampled focussed on substituting or augmenting learning through technology, with relatively few studies using technology to modify or redefine what HPE is through the use of technology. Of more concern was the lack of theoretical justification for pedagogical improvement, including transformation, underpinning the majority of studies.

Conclusions

While all kinds of technology use in learning have their place, the next step for HPE is the robust use of technology aiming to lead transformation. This should be guided by transformational educational theory and aligned with pedagogical context. We challenge HPE practitioners and scholars to work thoughtfully and with intent to enable transformation in education for future health professionals.
Nurses' lived experience of peacebuilding
Authors: Srof Brenda J. , Lagerwey Mary , Liechty Joe
Published: August 2023

Nursing has a unique opportunity to address issues of structural violence that contribute to poor health outcomes. Models for designing nursing care relative to the social determinants of health can be adapted from the discipline of peace studies and the phenomenon of peacebuilding. The aim of this qualitative study was to describe the lived experience of peacebuilding from the perspective of community or public health nurses. Interviews were conducted with eight participants. Attributes of the peacebuilder included fostering human relationships that value the inherent worth and dignity of others, nurturing a character of humility and moral courage, and contemplating the personal cost of engaging in prolonged processes of peacebuilding. Practices of peacebuilding included mediating conflict through multilayered processes, accompanying others to places of empowerment, and utilizing interdisciplinary teaching and learning to build capacity for change. Increasing an understanding of the lived experience of peacebuilding by nurses is relevant to nursing research, theory, and practice, and adds to a broader understanding of peacebuilding.
Liver fat as risk factor of hepatic and cardiometabolic diseases
Authors: Demir Münevver , Bornstein Stefan R. , Mantzoros Christos S. , Perakakis Nikolaos
Published: August 2023

Non‐alcoholic fatty liver disease (NAFLD) is a disorder characterized by excessive accumulation of fat in the liver that can progress to liver inflammation (non‐alcoholic steatohepatitis [NASH]), liver fibrosis, and cirrhosis. Although most efforts for drug development are focusing on the treatment of the latest stages of NAFLD, where significant fibrosis and NASH are present, findings from studies suggest that the amount of liver fat may be an important independent risk factor and/or predictor of development and progression of NAFLD and metabolic diseases. In this review, we first describe the current tools available for quantification of liver fat in humans and then present the clinical and pathophysiological evidence that link liver fat with NAFLD progression as well as with cardiometabolic diseases. Finally, we discuss current pharmacological and non‐pharmacological approaches to reduce liver fat and present open questions that have to be addressed in future studies.