bluuebunny/crossref_metadata_2025 huggingface dataset:
Administrative coding of frailty: Its association with clinical outcomes and resource use in kidney transplantation
Authors: Mallick Saad , Sakowitz Sara , Bakhtiyar Syed Shahyan , Chervu Nikhil , Valenzuela Alberto , Kim Shineui , Benharash Peyman
Published: December 2023

Introduction

Although not formalized into current risk assessment models, frailty has been associated with negative postoperative outcomes in many specialties. However, national analyses of the association between frailty and post‐transplant outcomes following kidney transplantation (KT) are lacking.

Methods

This was a retrospective cohort study of adults undergoing KT from 2016 to 2020 in the Nationwide Readmissions Databases. Frailty was defined using the Johns Hopkins Adjusted Clinical Groups frailty indicator.

Results

Of an estimated 95 765 patients undergoing KT during the study period, 4918 (5.1%) were frail. After risk adjustment, frail patients were associated with significantly higher odds of in‐hospital mortality (AOR 2.17, 95% CI: 1.33–3.57) compared to their non‐frail counterparts. Our findings indicate that frail patients had an average increase in postoperative hospital stay of 1.44 days, a $2300 increase in hospitalization costs, as well as higher odds of developing a major perioperative complication as compared to their non‐frail counterparts. Frailty was also associated with greater adjusted risk of non‐home discharge.

Conclusions

Frailty, as identified by administrative coding, is independently associated with worse surgical outcomes, including increased mortality and resource use, in adults undergoing KT. Given the already limited donor organ pool, novel efforts are needed to ensure adequate optimization and timely post‐transplantation care of the growing frail cohort undergoing KT.
Day 100 Natural Killer Cell/CD14+HLA‐DRDIMratio and survival in lymphoma post‐autologous peripheral blood hematopoietic stem cell transplantation
Authors: Porrata Luis F. , Ansell Stephen M. , Micallef Ivana N. , Johnston Patrick B. , Villasboas Jose C. , Paludo Jonas , Durani Urshila , Markovic Svetomir N.
Published: December 2023

Introduction

The infusion of autograft Natural Killer Cells (NKC)/CD14+HLA‐DRDIMratio is a predictor of survival in lymphoma patients undergoing autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT). This study evaluated if the Day 100 NKC/CD14+HLA‐DRDIMratio still functions as a prognostic immune‐biomarker.

Methods

This was a retrospective, single‐institution, cohort analysis including 107 patients in this study that had clinical assessment at Day 100 post‐APBHSCT from our prior phase III trial. We evaluated the prognostic ability of the Day 100 NKC/CD14+HLA‐DRDIMratio to predict overall survival (OS) and progression‐free survival (PFS) using Cox regression model for outcome analysis and survival by Kaplan–Meier method.

Results

The median follow‐up from day 100 was 94.7 months (range 4.83–158.1 months) for the entire cohort. Patients with a Day 100 NKC/CD14+HLA‐DRDIMratio ≥1.67 experienced better OS and PFS versus those with a Day 100 NKC/CD14+HLA‐DRDIMratio <1.67: median OS was not reached versus 49.7 months, the 5‐year OS rates were 91% (95% CI, 81%–96%) versus 40% (95% CI, 27%–55%),p < .0001, respectively; and median PFS was not reached versus 23.5 months, the 5‐year PFS rates were 66% (95% CI, 55%–81%) versus 21% (95% CI, 15%–40%),p < .0001, respectively. Day 100 NKC/CD14+HLA‐DRDIMratio was an independent predictor for OS and PFS in the multivariate analysis.

Conclusions

Day 100 NKC/CD14+HLA‐DRDIMratio is a prognostic immune‐biomarker in lymphoma patients post‐ APBHSCT.
Utilizing geometric morphometrics to investigate gene function during organ growth: Insights through the study of beetle horn shape allometry
Authors: Rohner Patrick T. , Hu Yonggang , Moczek Armin P.
Published: December 2023

Static allometry is a major component of morphological variation. Much of the literature on the development of allometry investigates how functional perturbations of diverse pathways affect the relationship between trait size and body size. Often, this is done with the explicit objective to identify developmental mechanisms that enable the sensing of organ size and the regulation of relative growth. However, changes in relative trait size can also be brought about by a range of other distinctly different developmental processes, such as changes in patterning or tissue folding, yet standard univariate biometric approaches are usually unable to distinguish among alternative explanations. Here, we utilize geometric morphometrics to investigate the degree to which functional genetic manipulations known to affect the size of dung beetle horns also recapitulate the effect of horn shape allometry. We reasoned that the knockdown phenotypes of pathways governing relative growth should closely resemble shape variation induced by natural allometric variation. In contrast, we predicted that if genes primarily affect alternative developmental processes, knockdown effects should align poorly with shape allometry. We find that the knockdown effects of several genes (e.g., doublesex, Foxo) indeed closely aligned with shape allometry, indicating that their corresponding pathways may indeed function primarily in the regulation of relative trait growth. In contrast, other knockdown effects (e.g., Distal‐less, dachs) failed to align with allometry, implicating these pathways in potentially scaling‐independent processes. Our findings moderate the interpretation of studies focusing on trait length and highlight the usefulness of multivariate approaches to study allometry and phenotypic plasticity.
‘The same contract that is suitable for your Excellency’: Immigration and emulation in the adoption of sharecropping‐cum‐debt arrangements in Brazil (1835‒80)
Authors: Witzel de Souza Bruno Gabriel
Published: December 2023

This paper studies the history of contractual choice in coffee plantations of São Paulo, Brazil. It focuses on the consolidation of non‐captive labour markets in the early phases of the transition from slavery in the country, particularly in the 1840s–50s. Vis‐à‐vis the alternatives of fixed rents and fixed payments per time worked or piece rates, the paper examines the rationale for the adoption of sharecropping arrangements with European bonded labourers. New archival evidence suggests that sharecropping had no obvious productivity advantage over alternative labour–rental arrangements in this period, and that the adoption of sharecropping arrangements resulted from the positional advantage of its first proposers, who influenced later choices of contractual design. A credit‐labour tie‐up long outlived the original sharecropping arrangements, in turn allowing for the immigration of poor and credit‐constrained Europeans, paving the way to insert Brazil into the circuits of mass migration without promoting institutional reforms to attract non‐bonded immigrants.
Pharmacokinetics of d‐ and l‐norfenfluramine following their administration as individual enantiomers in rats
Authors: Erenburg Natalia , Hamed Roa'a , Shaul Chanan , Barasch Dinorah , Perucca Emilio , Bialer Meir
Published: December 2023

The effect of fenfluramine and norfenfluramine enantiomers in rodent seizure models and their correlation with the pharmacokinetics of d‐ and l‐fenfluramine in rats have been reported recently. To complement these findings, we investigated the pharmacokinetics of d‐ and l‐ norfenfluramine in rat plasma and brain. Sprague‐Dawley rats were injected intraperitoneally with 20 mg/kg and 1 mg/kg l‐ norfenfluramine. A 1 mg/kg dose of d‐norfenfluramine was used because higher doses caused severe toxicity. The concentration of each enantiomer in plasma and brain was determined at different time points by liquid chromatography/mass spectrometry. Pharmacokinetic parameters were compared between norfenfluramine enantiomers, and with those reported previously for fenfluramine enantiomers after a 20 mg/kg, i.p., dose. All enantiomers were absorbed rapidly and eliminated, with half‐lives ranging from 0.9 h (l‐fenfluramine) to 6.1 h (l‐ norfenfluramine, 20 mg/kg) in plasma, and from 3.6 h (d‐fenfluramine) to 8.0 h (l‐fenfluramine) in brain. Brain‐to‐plasma concentration ratios ranged from 15.4 (d‐fenfluramine) to 27.6 (d‐norfenfluramine), indicating extensive brain penetration. The fraction of d‐ and l‐fenfluramine metabolized to norfenfluramine was estimated to be close to unity. This work is part of ongoing investigations to determine the potential value of developing enantiomerically pure l‐fenfluramine or l‐norfenfluramine as follow‐up compounds to the marketed racemic fenfluramine.
Effect of Bacille‐Calmette‐Guerin vaccine against rotenone‐induced Parkinson's disease: Role of neuroinflammation and neurotransmitters
Authors: Yedke Narhari Gangaram , Soni Divya , Kumar Puneet
Published: December 2023

Background

Parkinson's disease (PD) is an extrapyramidal movement disorder associated with a hypokinetic condition generated by impairment in dopaminergic neuronal viability in the nigrostriatal region of the brain. Current medications can only provide symptomatic management; to date, no permanent cure is available. To compensate for this lacuna, researchers are gaining interest in antigen‐based therapy, and Bacille‐Calmette‐Guerin (BCG) is one of the vaccines with a high safety margin that acts by stimulating immunoreactive T‐cells in the CNS and reducing expression of pro‐inflammatory cytokines including interleukin (IL)‐1β and tumor necrotic factor (TNF‐α) to produce neuroprotection. A previous study reported that BCG exerts a neuroprotective effect against several neurodegenerative disorders, such as Alzheimer's disease.

Objective

The objective of this study is to explore the neuroprotective effect of the BCG vaccine against the rotenone model of PD.

Methods

Rotenone (1.5 mg/kg, s.c) for 28 days, and BCG vaccine (2 × 107 cfu, i.p) single dose was injected to rats, and behavioral assessments were performed on the 21st and 28th day. On the 29th day, rats were sacrificed, and brains were isolated for biochemical and neurochemical estimation.

Results

BCG vaccine significantly restored rotenone‐induced motor deficits (open field test, narrow beam walk, and rotarod), biochemical levels (GSH, SOD, catalase, MDA, and nitrite), neurotransmitters (dopamine, 5‐hydroxy tryptamine, norepinephrine, 3,4‐dihydroxyphenylacetic acid, hemovanillic acid, and 5‐hydroxy indoleacetic acid), and levels of inflammatory cytokines (IL‐1β and TNF‐α) in the striatum. It also prevents histopathological changes by reducing eosinophilic lesions in the striatum.

Conclusion

From the results, we conclude that BCG vaccine showed neuroprotection through antioxidant and anti‐inflammatory effect. Thus, in the future, it can be used as a neuroprotective agent for other neurological disorders, including PD.
Community size‐spectra applied to recreational freshwater fisheries in Puerto Rican reservoirs
Authors: Murry Brent A. , Olmeda María de Lourdes , Lilyestrom Craig , Adams Daniel S. , Adase Katherine , García‐Bermudez Miguel
Published: December 2023

We developed a management framework based on community size‐spectra (CSS) to establish targets to maximize desirable gamefish. We evaluated the influence of relative abundance of fish functional groups and watershed characteristics on the slope of the CSS or ecological efficiency. Both ecological efficiency and capacity were strongly influenced by relative abundance of fish functional groups and the degree of water level variation. Steeper slopes indicated overfished gamefish populations, whereas flatter slopes indicated systems dominated by undesirable invasive large‐bodied low trophic position fish. We hypothesize that a desirable fishery would have a target range of CSS slopes that provides a deterministic community‐based framework of predictable responses to environmental and food web changes that can be used to evaluate outcomes of management actions and a means to assess annual progress toward desirable conditions.
How much organic carbon could the soil store? The carbon sequestration potential of Australian soil
Authors: Viscarra Rossel R. A. , Webster R. , Zhang M. , Shen Z. , Dixon K. , Wang Y.‐P. , Walden L.
Published: December 2023

Soil is a huge carbon (C) reservoir, but where and how much extra C can be stored is unknown. Current methods to estimate the maximum amount of mineral‐associated organic carbon (MAOC) stabilized in the fine fraction (clay + silt, ) fit through the MAOC versus clay + silt relationship, not their maxima, making their estimates more uncertain and unreliable. We need a function that ‘envelopes’ that relationship. Here, using 5089 observations, we estimated that the uppermost 30 cm of Australian soil holds 13 Gt (10–18 Gt) of MAOC. We then fitted frontier lines, by soil type, to the relationship between MAOC and the percentage of clay + silt to estimate the maximum amounts of MAOC that Australian soils could store in their current environments, and calculated the MAOC deficit, or C sequestration potential. We propagated the uncertainties from the frontier line fitting and mapped the estimates of these values over Australia using machine learning and kriging with external drift. The maps show regions where the soil is more in MAOC deficit and has greater sequestration potential. The modelling shows that the variation over the whole continent is determined mainly by climate, linked to vegetation and soil mineralogy. We find that the MAOC deficit in Australian soil is 40 Gt (25–60 Gt). The deficit in the vast rangelands is 20.84 Gt (13.97–29.70 Gt) and the deficit in cropping soil is 1.63 Gt (1.12–2.32 Gt). Management could increase C sequestration in these regions if the climate allowed it. Our findings provide new information on the C sequestration potential of Australian soils and highlight priority regions for soil management. Australia could benefit environmentally, socially and economically by unlocking even a tiny portion of its soil's C sequestration potential.
Soil fertility shapes fire activity across Mediterranean‐type climate regions
Authors: Paula Susana , Ramírez Diego P. , Estay Sergio , Pausas Juli G.
Published: December 2023

Aim

To quantify the role of soil fertility in the spatial variability of fire activity and to identify the mechanisms that drive this variability.

Location

The five Mediterranean‐type climate regions of the world.

Time Period

2002–present.

Major Taxa Studied

Terrestrial plants.

Methods

We compiled remotely sensed data on fire activity, climate, net primary productivity and chemical soil properties for bioclimatically homogeneous zones within the five Mediterranean‐type climate regions of the world. Putative direct and indirect effects of the environmental variables on fire activity were evaluated through structural equation modelling.

Results

Fire activity increased with net primary productivity, as expected for ecosystems with fuel‐limited fire regimes. Soil acidity and the concentration of exchangeable aluminium also increased fire activity, supporting the idea that low fertility promotes plant characteristics that favour fire initiation and spread.

Main Conclusions

Our research supports a positive relationship between wildfires and low soil fertility in Mediterranean‐type climate regions across the globe. Therefore, soil fertility should be incorporated into models predicting future fires in a warming world.
Are larger cities more central in urban networks: A meta‐analysis
Authors: Li Xiaomeng , Neal Zachary P.
Published: December 2023

As cities develop more and longer‐range external relations, some have challenged the long‐standing notion that population size indicates a city's power in its urban system. But are population size and network centrality really independent properties in practice, or do larger cities tend to be more central in urban networks? To answer this question, we conducted a systematic literature search and meta‐analysed 41 reported correlations between city size and degree centrality. The results show that population size and degree centrality are significantly and positively correlated for cities across various urban systems (r = 0.77), but the correlation varies by network scale and type. The size‐centrality association is weaker for global economic and transportation networks
(r = 0.43), and stronger for non‐global social and communication networks (r = 0.91). This clarifies seemingly contradictory predictions in the literature regarding the association betweensize and centrality for cities.
Transparency's impact on the professionalization of government
Authors: Batista Mariana , Michener Gregory
Published: December 2023

Freedom of information (FOI) laws are known to expose governmental weaknesses, but do they improve the structural workings of public administration, professionalizing governance? This study examines FOI's effect on a cornerstone of effective governance—bureaucratic hiring. Using coarsened matching methods to compare over 5400 municipalities in Brazil—approximately half possessing FOI regulations and half without—we identify significant reductions in discretionary patronage‐based appointments. Municipalities with FOI regulations reduce both higher level “political control” and lower‐level “electoral rewards” hires. Our explanation, tentatively supported by a comparison of early versus late FOI adopters, centers on sequencing: in the short term, leaders view FOI as a supplement to administrative control and thus reduce higher‐level hires. As FOI becomes more institutionalized and exposures more probable, leaders reduce lower‐level hires. Contributing to scholarship on transparency and bureaucracies, our results enjoin policymakers to double‐down on commitments to FOI policies.
The shame of sexual violence towards women in rural areas
Authors: Jones Rikki , Usher Kim , Rice Kylie , Morley Louise , Durkin Joanne
Published: December 2023

This perspective paper presents a discussion around the issues of sexual violence (SV) in rural and remote areas and the associated discourses of shame. The authors propose that shame of SV adds additional trauma to survivors, further impacting survivors' mental health which may be exacerbated in rural areas. Shame is a complex emotion that can result in increased feelings of guilt, humiliation, and embarrassment. Shame has been identified as an underlying risk factor and a mechanism for post‐assault mental health problems. We propose it can be particularly pronounced for women subjected to sexual assault in rural or remote areas. This paper will explore the link between SV and shame, explain how shame attached to SV may be used as an informal social control mechanism for women, particularly in rural and remote areas, and discuss the role of health practitioners, particularly mental health nurses, who play a key role in supporting people impacted by SV. SV is an insidious social phenomenon that can have profound consequences for individuals, families, and communities. Addressing shame and stigma is a crucial component of supporting survivors of SV in rural and remote areas. There is a need for targeted community‐led interventions and responsive support services to address the complex and multifaceted issues contributing to SV in rural and remote communities.
Leisure crafting and work engagement among Chinese ICU nurses: The multiple mediation effect of recovery experience and humanistic care ability
Authors: Liu Qingwei , Zhao Li , Guo Xiaojing , Zhang Yuchen , Xin Chen , Gai Yubiao
Published: December 2023

Aims

Based on the conservation of resources theory, this study explored the intermediary role of intensive care unit (ICU) nurses’ recovery experience and humanistic care ability between leisure crafting and work engagement.

Background

As the ICU is an important life‐saving department, the level of work engagement of nurses directly affect the quality of life and health outcomes of patients. Actively seeking countermeasures to improve the work engagement level of ICU nurses is of great significance to enhancing the nursing quality of the ICU. According to the theory of resource conservation, the resources owned by individuals are limited and must be replenished promptly and effectively to maintain relatively stable physical, mental, and working states. Therefore, determining ways for ICU nurses to supplement the consumed resources effectively and efficiently in a limited time to maintain a high level of work engagement is the main concern of this study.

Methods

In this cross‐sectional study from January 2023 to March 2023, 478 ICU nurses were recruited by convenience sampling. The survey tools included the Leisure Crafting Scale, the Utrecht Work Engagement Scale‐9, the Caring Ability Inventory, and the Recovery Experience Questionnaire. Descriptive data and Pearson correlation coefficients were analyzed via SPSS 26.0 (IBM Corp.). PROCESS v4.0 (by Andrew F. Hayes) Macro Model 6 was applied to analyze the serial multiple mediator models. We used the STROBE checklist to report the results.

Results

First, the results showed that leisure crafting, humanistic care ability, and recovery experience were positively correlated with work engagement. Second, recovery experience and humanistic care ability played a partially mediating role between leisure crafting and work engagement, respectively. Third, recovery experience and humanistic care ability also had a serial mediation effect between leisure crafting and work engagement.

Conclusion

The findings of the study indicated that improving nurses’ active control of leisure time may have particularly positive effects on ICU nurses’ work engagement through increasing recovery experience and humanistic care ability.

Implications for nursing and nursing policy

Administrators can formulate intervention measures to improve the leisure crafting level of ICU nurses, promote work–life balance, which enhances recovery and supports engagement with patient‐focused humanistic care, and have a positive impact on the work engagement of ICU nurses.
Computational complexity and linear formulations for optimizing the location of shared mobility stations
Authors: Monteiro Cristiano Martins , dos Santos Vinicius Fernandes , Davis Junior Clodoveu Augusto
Published: December 2023

Properly planned shared mobility services can be attractive even for who owns and drives a private vehicle, but would consider not owning it anymore if a cheaper, more sustainable, and accessible transport service is available. However, planning such services may become computationally intractable as demand and coverage widen, requiring different methods for optimizing them. This work contextualizes the computational challenges in defining station locations for shared mobility services; proves the NP‐hardness of optimizing the exact locations for shared mobility stations; proves the NP‐hardness of selecting street segments to have shared mobility stations; proposes mixed‐integer linear programming formulations for both problems; proposes and compares the performance of these formulations to two heuristics; and applies these formulations to the road network of the metropolitan region of São Paulo in Brazil. Results show the trade‐off between computational efforts and the precision of optimal solutions by choosing which problem to solve.
Proactive berth scheduling with data‐driven buffer time in container terminals
Authors: Woo Sung Hun , Park Hyun Ji , Cho Sung Won , Kim Ki Hong
Published: December 2023

Global shipment volumes have been increasing due to changes in the business environment of e‐commerce and manufacturing. Consequently, container vessels carry more cargo for international trade, increasing uncertainties in terminal management. Terminal operators manage terminals by establishing a proactive schedule that responds to disruptions such as vessel delays, and the introduction of buffer time is a representative proactive strategy. In this study, by analyzing historical delay data with machine learning, we propose data‐driven buffer times to consider the heterogeneous arrival uncertainty of vessels. Thus, we proactive scheduling with data‐driven buffer times according to the desired robustness levels. This is a novel study on berth scheduling that applies data mining approaches to improve operations research techniques. Numerical experiments were conducted on the berth scheduling with time‐invariant quay crane assignment using real‐life data to validate the effectiveness of the proposed method. These experimental results revealed that applying the data‐driven buffer time could effectively reduce the cost incurred at the terminal by balancing baseline and recovery costs. In addition, our proposed methodology ensured the quality of the solution compared with a stochastic method and reduced the computational burden of a stochastic problem by using the data‐driven buffer times obtained prior to the solution construction. Therefore, the proposed method can be introduced into terminal operations to overcome the deficiencies of traditional approaches in terms of academic perspective.
Older people's experiences of elder abuse in residential care settings: A scoping review
Authors: Duffy Anita , Connolly Michael , Browne Freda
Published: December 2023

Background

Elder abuse is a global human rights issue, particularly in residential care settings where there is limited understanding of older people's experiences of this phenomenon. This scoping review aims to map and describe the existing literature on this phenomenon.

Methods

Using Arksey and O'Malley's scoping review methodology, further developed by Levac et al. and the Joanna Briggs Institute, a systematic search of six databases was conducted to identify relevant studies published from inception to January 2023. Studies were included if they focused on older people's experience of abuse within residential care settings. A comprehensive data extraction process was employed to identify key themes from the included studies.

Results

The initial search yielded a total of 3701 articles of which eight met the inclusion criteria. The findings revealed a range of abusive experiences encountered by older people living in residential care settings, including psychological, physical, financial, neglect and sexual abuse. The common attributes of residents vulnerable to abuse were evident throughout each of the studies. Finally, the theme of organizational neglect was apparent through the absence of effective safeguarding measures in the included studies. The findings revealed the insufficient implementation of safeguarding measures increases the risk of abuse among residents.

Conclusion

This scoping review highlights the limited research on the experiences of older people who have encountered elder abuse in residential care settings. The findings stress the need for further research exploring the complex interplay of factors contributing to elder abuse within aged care settings. The insights gained from this scoping review can inform the development of comprehensive safeguarding strategies to prevent and address elder abuse in residential care settings, promoting the well‐being and safety of older people.

Patient or Public Contribution

This project is a scoping review of the literature; therefore, no patient or public contribution was deemed necessary.

What this paper contributes to the wider global community

Most research on elder abuse has been conducted in the community rather than in Residential Care Settings where there is a limited understanding of older people’s experiences of abuse within the published literature.

The scoping review highlights the presence of inadequate safeguarding strategies in Residential Care Settings within the reviewed studies, providing recommendations for developing and improving safeguarding measures in Residential Care Settings to prevent abuse, neglect, and harm in the future.
Antioxidant therapy against TGF‐β/SMAD pathway involved in organ fibrosis
Authors: Ghafouri‐Fard Soudeh , Askari Arian , Shoorei Hamed , Seify Mohammad , Koohestanidehaghi Yeganeh , Hussen Bashdar Mahmud , Taheri Mohammad , Samsami Majid
Published: December 2023

Fibrosis refers to excessive build‐up of scar tissue and extracellular matrix components in different organs. In recent years, it has been revealed that different cytokines and chemokines, especially Transforming growth factor beta (TGF‐β) is involved in the pathogenesis of fibrosis. It has been shown that TGF‐β is upregulated in fibrotic tissues, and contributes to fibrosis by mediating pathways that are related to matrix preservation and fibroblasts differentiation. There is no doubt that antioxidants protect against different inflammatory conditions by reversing the effects of nitrogen, oxygen and sulfur‐based reactive elements. Oxidative stress has a direct impact on chronic inflammation, and as results, prolonged inflammation ultimately results in fibrosis. Different types of antioxidants, in the forms of vitamins, natural compounds or synthetic ones, have been proven to be beneficial in the protection against fibrotic conditions both in vitro and in vivo. In this study, we reviewed the role of different compounds with antioxidant activity in induction or inhibition of TGF‐β/SMAD signalling pathway, with regard to different fibrotic conditions such as gastro‐intestinal fibrosis, cardiac fibrosis, pulmonary fibrosis, skin fibrosis, renal fibrosis and also some rare cases of fibrosis, both in animal models and cell lines.
Role of AT‐rich interaction domain 1A in gastric cancer immunotherapy: Preclinical and clinical perspectives
Authors: Zhang Xuemei , Zhang Youzhi , Zhang Qiaoyun , Lu Mengyao , Chen Yuan , Zhang Xiaoyu , Zhang Peng
Published: December 2023

The application of immune checkpoint inhibitor (ICI) using monoclonal antibodies has brought about a profound transformation in the clinical outcomes for patients grappling with advanced gastric cancer (GC). Nonetheless, despite these achievements, the quest for effective functional biomarkers for ICI therapy remains constrained. Recent research endeavours have shed light on the critical involvement of modified epigenetic regulators in the pathogenesis of gastric tumorigenesis, thus providing a glimpse into potential biomarkers. Among these regulatory factors, AT‐rich interaction domain 1A (ARID1A), a pivotal constituent of the switch/sucrose non‐fermentable (SWI/SNF) complex, has emerged as a promising candidate. Investigations have unveiled the pivotal role of ARID1A in bridging the gap between genome instability and the reconfiguration of the tumour immune microenvironment, culminating in an enhanced response to ICI within the landscape of gastric cancer treatment. This all‐encompassing review aims to dissect the potential of ARID1A as a valuable biomarker for immunotherapeutic approaches in gastric cancer, drawing from insights garnered from both preclinical experimentation and clinical observations.
Association of RPS26 gene polymorphism with different types of diabetes in Chinese individuals
Authors: Song Rong , Xie Lingxiang , Ding Jin , Chen Yan , Zou Hailan , Pang Haipeng , Peng Yiman , Xia Ying , Xie Zhiguo , Li Xia , Xiao Yang , Zhou Zhiguang , Hu Jingyi
Published: December 2023

Aims/Introduction

Different types of diabetes show distinct genetic characteristics, but the specific genetic susceptibility factors remain unclear. Our study aimed to explore the associations between the ribosomal protein S26 (RPS26) gene rs1131017 polymorphisms and susceptibility to type 1 diabetes mellitus, latent autoimmune diabetes in adults (LADA) and type 2 diabetes mellitus in the Chinese Han population, and their correlations with clinical features.

Materials and Methods

Genotyping of the rs1131017 variant was carried out for 1,006 type 1 diabetes mellitus patients, 210 LADA patients, 642 type 2 diabetes mellitus patients and 2,099 control individuals.

Results

We found that the rs1131017 C allele was a risk locus for both type 1 diabetes mellitus and LADA (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.33–1.69, P < 0.001; OR 1.31, 95% CI 1.04–1.64, P = 0.021, respectively). Nevertheless, this association was not found for type 2 diabetes mellitus. Carrying the C allele genotype was associated with a lower postprandial C‐peptide for type 1 diabetes mellitus (OR 1.41, 95% CI 1.11–1.80, P = 0.006) and lower fasting C‐peptide for LADA (OR 1.55, 95% CI 1.01–2.38, P = 0.047). Interestingly, a lower GC frequency was noted for LADA than for type 1 diabetes mellitus, regardless of classification based on age at diagnosis, C‐peptide or glutamic acid decarboxylase antibody positivity.

Conclusions

The RPS26 polymorphism was associated with susceptibility and clinical characteristics of type 1 diabetes mellitus and LADA in the Chinese population, but was not related to type 2 diabetes mellitus. Thus, it might serve as a novel biomarker for particular types of diabetes.
Baricitinib treatment rapidly improves the four signs of atopic dermatitis assessed by Eczema Area and Severity Index (EASI) clinical subscores
Authors: Wollenberg Andreas , Simon Dagmar , Kulthanan Kanokvalai , Figueras‐Nart Ignasi , Misery Laurent , Tangsirisap Nithi , Spina Lara , Lu Na , Grond Susanne , Eyerich Kilian
Published: December 2023

Background

Baricitinib treatment in adults with moderate‐to‐severe atopic dermatitis (AD) has demonstrated rapid improvements in itch as well as AD sign severity and affected body surface area as assessed by the Eczema Area and Severity Index (EASI) total score, whether administered as monotherapy or in combination with topical corticosteroids (TCS). As EASI clinical signs differ in time course and associated antecedents, the effects of baricitinib on each individual clinical sign are of interest.

Objectives

In this post hoc analysis, we aimed to investigate the effects of baricitinib on individual EASI subscores, namely excoriation, oedema/papulation, erythema and lichenification, in both monotherapy and TCS combination therapy trials.

Methods

We analysed the percent change from baseline in individual EASI subscores from three phase‐III, double‐blind, 16‐week trials of baricitinib in monotherapy (BREEZE‐AD1/BREEZE‐AD2) and TCS combination therapy (BREEZE‐AD7) cohorts via mixed model repeated measures (MMRM).

Results

Baricitinib 4 mg showed rapid and sustained improvements in all four clinical signs in both cohorts. Significant effects emerged at week 1 for excoriation, oedema/papulation and erythema scores in monotherapy (p < 0.001) and TCS combination therapy (p < 0.001, p < 0.01, p < 0.001), plateaued at week 4, and remained significant versus placebo through week 16. The effect on lichenification scores also emerged early, at week 1 in monotherapy (p < 0.05) and week 2 in combination therapy (p < 0.001), with scores continuously improving without a clear plateau. Effect magnitude was highest in excoriation scores, exhibiting near‐maximal reduction in week 1 of monotherapy and remaining highest across all timepoints in combination therapy.

Conclusions

Rapid and sustained improvements were observed across clinical signs of inflammation and particularly on excoriation following baricitinib treatment. Our findings suggest that selective inhibition of janus kinases 1 and 2 leads to rapid and sustained control of skin inflammation, and that rapid reductions in itch translate into early disruption of the itch‐scratch cycle.
The role of dietary vitamin A in mechanisms of cataract development in the teleost lumpfish (Cyclopterus lumpus L)
Authors: Deering Margret J. , Paradis Hélène , Ahmad Raahyma , Al‐Mehiawi Adil S. , Gendron Robert L.
Published: December 2023

Lumpfish (Cyclopterus lumpus L) are highly prone to cataract development in the wild and in culture. There is evidence that cataract in farmed fish is related to nutrition. However, both the nutrients and the mechanisms involved in cataract development in lumpfish are not clear. Here we investigated the mechanisms involved and the role of dietary vitamin A in cataract development in a cultured lumpfish population. Cultured lumpfish were fed three diets differing only in vitamin A supplementation level (5000, 15,000 and 120,000 IU/kg) over an 18‐month period, and fish weight, cataract frequencies and severities were determined. Western blotting and immunohistochemistry were performed on lens tissue to measure the levels of oxidative stress, and apoptosis. The lowest levels of vitamin A significantly reduced cataract frequencies in adult lumpfish and resulted in less severe cataract and increased weight in males. Oxidative stress levels in the lens were positively correlated with vitamin A intake. Apoptosis was observed at high levels in lenses with severe cataract. Oxidative stress and apoptosis levels were the highest in regions of the lens with severe, advanced cataract pathology when compared to regions with no visible pathology. These results suggest that higher vitamin A intake contributes to cataract development through an oxidative stress pathway, and that both oxidative stress and apoptosis are involved in advanced stages of cataract in lumpfish.
Association between burnout and post‐traumatic stress disorder among frontline nurse during COVID‐19 pandemic: A moderated mediation analysis
Authors: Liang Leilei , Hu Yuanchao , Fei Junsong , Yuan Tongshuang , Gao Ren , Yue Jingyi , Song Qianqian , Zhao Xixi , Mei Songli
Published: December 2023

Aims and Objectives

The aim of this study was to investigate the relationship between burnout and post‐traumatic stress disorder (PTSD) among frontline nurses who went to assist the epidemic situation in Wuhan, China, during the outbreak in 2020. The study also explored the mediating role of depression and the moderating role of age in the main relationship.

Background

The relationship between burnout and PTSD in nurse has rarely been investigated in the context of the COVID‐19 pandemic. Understand the relationship between these variables can provide empirical evidence for developing interventions and protocols that improve the health of nurses in future public health emergencies.

Design

An online cross‐sectional survey of targeted local 327 nurses who went to assist the COVID‐19 epidemic situation in Wuhan during the initial outbreak.

Methods

This study was conducted in August 2020, the burnout scale, the PTSD scale and the depression scale were used to survey participants. The moderated mediation model was used to test research hypotheses.

Results

Burnout could affect the PTSD symptoms in nursing staffs and depression could mediate this relationship. Age moderated the relationship between burnout/depression and PTSD, and the effects was strong and significant among younger participants in the relationship between burnout and PTSD.

Conclusions

Burnout was identified as a core risk factor of PTSD in nurses. Depression and age played significant roles in the relationship between burnout and PTSD.

Relevance to Clinical Practice

PTSD, as a symptom that manifests after experiencing a stressful event, should be a key concern among frontline healthcare professionals. This study suggests that PTSD in nurses can be further reduced by reducing burnout. Attention should also be paid to the PTSD status of nurses of different age groups.

Patient or Public Contribution

Patients and the public were not involved in the design and implementation of this study. Frontline nurses completed an online questionnaire for this study.
Attitudes of patients with schizophrenia spectrum or bipolar disorders towards medication self‐management during hospitalisation
Authors: Loots Elke , Dilles Tinne , Van Rompaey Bart , Morrens Manuel
Published: December 2023

Background

Medication self‐management (MSM) is defined as a person's ability to cope with medication treatment for a chronic condition, along with the associated physical and psychosocial effects that the medication causes in their daily lives. For many patients, it is important to be able to self‐manage their medication successfully, as they will often be expected to do after discharge.

Aim

The aim of this study was to describe the willingness and attitudes of patients with schizophrenia spectrum or bipolar disorders regarding MSM during hospital admission. A secondary aim was to identify various factors associated with patient willingness to participate in MSM and to describe their assumptions concerning needs and necessary conditions, as well as their attitudes towards their medication.

Methods

A multicentre, quantitative cross‐sectional observational design was used to study the willingness and attitudes of psychiatric patients regarding MSM during hospitalisation. The study adhered to guidelines for Strengthening the Reporting of Observational Studies in Epidemiology (STROBE).

Results

In this study, 84 patients, of which 43 were patients with schizophrenia spectrum disorders and 41 were patients with bipolar disorders, participated. A majority of the patients (81%) were willing to participate in MSM during their hospitalisation. Analysis revealed patients are more willing to MSM if they are younger (r = −.417, p < .001) and a decreasing number of medicines (r = −.373, p = .003). Patients' willingness was positively associated with the extent of support by significant others during and after hospitalisation (Pearson's r = .298, p = .011). Patients were convinced that they would take their medication more correctly if MSM were to be allowed during hospitalisation (65%).

Conclusion

Most of the patients were willing to self‐manage their medication during hospitalisation, however, under specific conditions such as being motivated to take their medication correctly and to understand the benefits of their medication.

Relevance to Clinical Practice

From a policy point of view, our study provided useful insights into how patients look at MSM to enable the development of future strategies. Since patients are willing to self‐manage their medication during hospitalisation, this may facilitate its implementation.

Patient contribution

Patients were recruited for this study. Participation was voluntary, and signed informed consent was obtained from all participants prior to the questionnaire.
Polioencephalopathy in Eurasier dogs
Authors: Rawson Faye , Christen Matthias , Rose Jeremy , Paran Emilie , Leeb Tosso , Fadda Angela
Published: December 2023

Background

Polioencephalopathies secondary to inborn errors of metabolism have been described in dogs, but few genetically characterized.

Objectives

Clinically and genetically characterize polioencephalopathy in a family of Eurasier dogs.

Animals

Three Eurasier dogs (littermates) presented with early onset movement disorders (9 weeks in 2, 4‐6 months in 1). Progressive gait abnormalities were detected in 2 of the dogs, persistent divergent strabismus in 1, whereas consciousness and behavior remained intact in all dogs. One dog was euthanized at 25 months.

Methods

Video footage was assessed in all dogs, and Dogs 1 and 2 had examinations and investigations performed. Whole genome sequencing of Dog 1 and further genetic analyses in the family were performed. A cohort of 115 Eurasier controls was genotyped for specific variants.

Results

Episodes were characterized by generalized ataxia, as well as a hypermetric thoracic limb gait, dystonia, and irregular flexion and extension movements of the thoracic limbs. Magnetic resonance imaging of the brain in Dogs 1 and 2 identified symmetrical, bilateral T2 and fluid attenuated inversion recovery hyperintense, T1 hypo to isointense, nonenhancing lesions of the caudate nucleus, lateral and medial geniculate nuclei, thalamus, hippocampus, rostral colliculus and mild generalized brain atrophy. Genetic analyses identified a homozygous mitochondrial trans‐2‐enoyl‐CoA reductase (MECR) missense variant in all 3 dogs, and a homozygous autophagy‐related gene 4D (ATG4D) missense variant in Dogs 1 and 2.

Conclusions and Clinical Importance

We describe a presumed hereditary and progressive polioencephalopathy in a family of Eurasier dogs. Further research is needed to establish the role of the MECR gene in dogs and the pathogenic effects of the detected variants.
Juvenile idiopathic epilepsy in Egyptian Arabian foals, a potential animal model of self‐limited epilepsy in children
Authors: Aleman Monica , Benini Ruba , Elestwani Sami , Vinardell Tatiana
Published: December 2023

Background

Juvenile idiopathic epilepsy (JIE) is categorized as a generalized epilepsy. Epilepsy classification entails electrocortical characterization and localization of epileptic discharges (ED) using electroencephalography (EEG).

Hypothesis/Objectives

Characterize epilepsy in Egyptian Arabian foals with JIE using EEG.

Animals

Sixty‐nine foals (JIE, 48; controls, 21).

Methods

Retrospective study. Inclusion criteria consisted of Egyptian Arabian foals: (1) JIE group diagnosed based on witnessed or recorded seizures, and neurological and EEG findings, and (2) control group of healthy nonepileptic age‐matched foals. Clinical data were obtained in 48 foals. Electroencephalography with photic stimulation was performed under standing sedation in 37 JIE foals and 21 controls.

Results

Abnormalities on EEG were found in 95% of epileptic foals (35 of 37) and in 3 of 21 control asymptomatic foals with affected siblings. Focal ED were detected predominantly in the central vertex with diffusion into the centroparietal or frontocentral regions (n = 35). Generalization of ED occurred in 14 JIE foals. Epileptic discharges commonly were seen during wakefulness (n = 27/37 JIE foals) and sedated sleep (n = 35/37 JIE foals; 3/21 controls). Photic stimulation triggered focal central ED in 15 of 21 JIE foals.

Conclusions and Clinical Importance

Juvenile idiopathic epilepsy has a focal onset of ED at the central vertex with spread resulting in clinical generalized tonic‐clonic seizures with facial motor activity and loss of consciousness. Electroencephalography with photic stimulation contributes to accurate phenotyping of epilepsy. Foals with this benign self‐limiting disorder might serve as a naturally occurring animal model for self‐limited epilepsy in children.
Environmental factors are the major drivers of macroinvertebrate assemblage structure in southern Brazilian coastal lakes
Authors: Mazzoni Aline Corrêa , Lanzer Rosane , Pires Mateus Marques , Schäfer Alois , Maltchik Leonardo , Stenert Cristina
Published: December 2023

Coastal freshwater lakes are distinctive landscape features in South America, and benthic macroinvertebrates are key to their ecological functioning. Identifying the main factors driving the assemblage structure of benthic macroinvertebrate is thus important for the development of management strategies in these ecosystems. However, studies on the drivers of macroinvertebrate assemblages are scarce in subtropical coastal lakes of the Neotropical region. Here, we evaluated the role of environmental (morphometric and water chemistry variables) and spatial factors in the assemblage structure of benthic macroinvertebrates in 36 coastal freshwater lakes in Brazil from 2008 to 2015. Macroinvertebrate family richness increased with ammonium, pH and water transparency, and decreased with nitrate content (slope ≈1 for all significant variables). Environmental factors explained most of the variation in macroinvertebrate composition (16%) compared to spatial ones (3.4%). In specific, Dugesiidae, Hydrobiidae, Corbiculidae, Sphaeromatidae, Noteridae, Hydropsychidae, Culicidae and Ceratopogonidae predominated in lakes with lower conductivity (<100 μS/cm) and higher water transparency (>1 m). Spatial factors summarized differences in macroinvertebrate assemblages between isolated and connected lakes. Although none of the lakes studied are directly impacted by organic pollution, our results suggest that benthic macroinvertebrate assemblages in subtropical coastal lakes are mostly structured by water chemistry, likely reflecting the major trends in land use along the study region (transition from agriculture to urban areas). We recommend that the conservation of macroinvertebrate biodiversity in southern Brazilian coastal lakes focus on the monitoring of water chemistry factors associated with human‐based land use.