bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel adjuvant formulation induces robust Th1/Th17 memory and mucosal recall responses in Non-Human Primates
Authors: Woodworth Joshua S , Contreras Vanessa , Christensen Dennis , Naninck Thibaut , Kahlaoui Nidhal , Gallouët Anne-Sophie , Langlois Sébastien , Burban Emma , Joly Candie , Gros Wesley , Dereuddre-Bosquet Nathalie , Morin Julie , Olsen Ming Liu , Rosenkrands Ida , Stein Ann-Kathrin , Wood Grith Krøyer , Follmann Frank , Lindenstrøm Thomas , LeGrand Roger , Pedersen Gabriel Kristian , Mortensen Rasmus
Published: February 2023

After clean drinking water, vaccination is the most impactful global health intervention. However, development of new vaccines against difficult-to-target diseases is hampered by the lack of diverse adjuvants for human use. Of particular interest, none of the currently available adjuvants induce Th17 cells. Here, we develop and test an improved liposomal adjuvant, termed CAF®10b, that incorporates a TLR-9 agonist. In a head-to-head study in non-human primates (NHPs), immunization with antigen adjuvanted with CAF®10b induced significantly increased antibody and cellular immune responses compared to previous CAF® adjuvants, already in clinical trials. This was not seen in the mouse model, demonstrating that adjuvant effects can be highly species specific. Importantly, intramuscular immunization of NHPs with CAF®10b induced robust Th17 responses that were observed in circulation half a year after vaccination. Furthermore, subsequent instillation of unadjuvanted antigen into the skin and lungs of these memory animals led to significant recall responses including transient local lung inflammation observed by Positron Emission Tomography-Computed Tomography (PET-CT), elevated antibody titers, and expanded systemic and local Th1 and Th17 responses, including >20% antigen-specific T cells in the bronchoalveolar lavage. Overall, CAF®10b demonstrated an adjuvant able to drive true memory antibody, Th1 and Th17 vaccine-responses across rodent and primate species, supporting its translational potential.
Computational Modelling of Immune Interaction and Epidermal Homeostasis in Psoriasis
Authors: Paramalingam Dinika , Li Bowen , Reynolds Nick J. , Zuliani Paolo
Published: February 2023

Psoriasis is an incurable chronic inflammatory skin disease characterised by immune cytokine-stimulated epidermal hyperproliferation. This results in the skin becoming red with scaly plaques that can appear anywhere on the body, decreasing the quality of life for patients. Previous modelling studies of psoriasis have been limited to 2D models and lacked cell-cell interactions. We have developed a 3D agent-based model of epidermal cell dynamics to gain insights into how immune cytokine stimuli induces hyperproliferation in psoriasis to better understand disease formation and structural changes. Three main keratinocytes, stem, transit-amplifying (TA), differentiated and T cells, are modelled with proliferation and division governed by various nutrients and immune cytokines. Each cell has a set of attributes (growth rate, division probability, position, etc) whose values are governed by processes such as monod-based cellular growth model, probability-based division based on calcium and cytokine concentration and various forces to form the epidermal layers. The model has 2 steady states, healthy (non-lesional) and psoriatic (lesional) skin. Transition from healthy to psoriatic state is triggered by a temporary cytokine stimulus which causes hyperproliferation to occur, a hallmark of psoriasis. This results in the deepening of rete ridges and thickening of the epidermal structure. Model outputs has been validated against population ratios of stem, TA, differentiated, and T cells, cell cycle and turnover times in vivo. The model simulates the structural properties of epidermis, including layer stratification, formation of wave-like rete ridges, change in epidermal height and length of rete ridges from healthy to psoriasis. This has provided some insights on the complex spatio-temporal changes when transitioning between the 2 steady states and how a shot of temporary cytokine stimulus can induce different severity of psoriasis and alters proliferation between healthy and psoriatic skin in line with known literature. This provides the basis to study different cytokine simulation variations of psoriasis development and tracking of cell proliferation in the lab. It also provides a baseline to model the effects of psoriasis treatments such as narrowband-ultraviolet B (NB-UVB) or biologics and predict potential treatment outcomes for patients.
Human Dermal Fibroblast Subpopulations and Epithelial Mesenchymal Transition Signals in Hidradenitis Suppurativa Tunnels are Normalized by Spleen Tyrosine Kinase Antagonism in Vivo
Authors: Flora A , Jepsen R , Kozera EK , Woods JA , Cains GD , Radzieta M , Jensen SO , Malone M , Frew JW
Published: February 2023

Hidradenitis Suppurativa is a chronic inflammatory disease of which the pathogenesis is incompletely understood. Dermal fibroblasts have been previously identified as a major source of inflammatory cytokines, however information pertaining to the characteristics of subpopulations of fibroblasts in HS remains unexplored. Using in silico-deconvolution of whole-tissue RNAseq, Nanostring gene expression panels and confirmatory immunohistochemistry we identified fibroblast subpopulations in HS tissue and their relationship to disease severity and lesion morphology. Gene signatures of SFRP2+ fibroblast subsets were increased in lesional tissue, with gene signatures of SFRP1+ fibroblast subsets decreased. SFRP2+ and CXCL12+ fibroblast numbers, measured by IHC, were increased in HS tissue, with greater numbers associated with epithelialized tunnels and Hurley Stage 3 disease. Pro-inflammatory CXCL12+ fibroblasts were also increased, with reductions in SFRP1+ fibroblasts compared to healthy controls. Evidence of Epithelial Mesenchymal Transition was seen via altered gene expression of SNAI2 and altered protein expression of ZEB1, TWIST1, Snail/Slug, E-Cadherin and N-Cadherin in HS lesional tissue. The greatest dysregulation of EMT associated proteins was seen in biopsies containing epithelialized tunnels. The use of the oral Spleen tyrosine Kinase inhibitor Fostamatinib significantly reduced expression of genes associated with chronic inflammation, fibroblast proliferation and migration suggesting a potential role for targeting fibroblast activity in HS.
Corporate collaborations, decarbonization and equity value creation
Authors: Schellhorn Carolin
Published: February 2023

Purpose

Opportunities for shareholder value creation from deep decarbonization in fossil fuel and related industries may be unlocked with a permanent change in corporate governance practices. The purpose of this study is to highlight the conceptual links between corporate collaborations, decarbonization and equity value creation to enable the large-scale reallocation of funds necessary to halve carbon emissions by the end of this decade.

Design/methodology/approach

Consistent with shareholder value maximization, the author uses the constant dividend growth framework to show that a permanent change in corporate governance practices can impact expectations of future cash flows and required rates of return. This study includes a simulation to explore how perpetual corporate collaborations on decarbonization that influence the key equity value drivers can add value to the equity of collaborative firms.

Findings

Perpetual corporate collaborations with key stakeholders focused on equity value drivers hold great potential for accelerating the reallocation of funds to low-carbon assets. Simulation results suggest that relatively small changes, especially in required rates of return, may result in substantial increases in equity values for collaborative leaders in deep decarbonization.

Originality/value

This study identifies new sources of shareholder value from long-term corporate collaborations with key stakeholders on deep decarbonization. A collaborative focus on important equity value drivers can attract capital also to hard-to-abate industries and initiate sharp cuts in carbon emissions. Corporate governance practices, thus, reformed render shareholder value creation incentive compatible with rapidly decarbonizing global supply chains, making it possible to meet climate action goals by 2030.
Does ownership concentration matter for the relationship between CEO characteristics and real earnings management: evidence from Jordan
Authors: Alhmood Mohammad , Shaari Hasnah , Al-Dhamari Redhwan , Sani Armaya’U Alhaji
Published: February 2023

Purpose

The current research inspects the moderation role of ownership concentration on chief executive officer (CEO) characteristics and real earnings management (REM) relationship in Jordan.

Design/methodology/approach

Driscoll–Kraay regressions were run using data from 348 firm-year observations for companies listed on the Amman Stock Exchange between 2013 and 2018.

Findings

Driscoll–Kraay regressions demonstrate that CEO experience, tenure and political connections improve REM practices. Ownership concentration diminishes and limits REM practices when combined with CEO experience, tenure and political connections, since all three have a negative and significant link with REM.

Research limitations/implications

Initial constraints include the study’s lack of generalisability due to a small number of CEO-related parameters. Second, critics of the ideal model for judging EM have a foreseeable flaw. No generally accepted model is perfect.

Practical implications

This study’s conclusions are crucial for industry participants, including companies, policymakers, investors and the general public. These findings will help investors, practitioners and regulators understand that businesses with significant ownership concentrations and experienced CEOs have superior earnings and low REM practises.

Social implications

The findings of this study have an optimistic impact on the existing body of knowledge. The current literature has yet to properly inspect the moderation role that ownership concentration has on the connotation between CEO characteristics and EM.

Originality/value

Despite several research studies in both developed and developing nations, ownership concentration has been almost virtually neglected. The current study could fill a hole in earlier research, rendering it a novel study.
Nurturing innovative culture in a healthcare organisation – Lessons from a Swedish case study
Authors: Andersson Thomas , Linnéusson Gary , Holmén Maria , Kjellsdotter Anna
Published: February 2023

Purpose

Healthcare organisations are often described as less innovative than other organisations, since organisational culture works against innovations. In this paper, the authors ask whether it has to be that way or whether is possible to nurture an innovative culture in a healthcare organisation. The aim of this paper is to describe and analyse nurturing an innovative culture within a healthcare organisation and how culture can support innovations in such a healthcare organisation.

Design/methodology/approach

Based on a qualitative case study of a healthcare unit that changed, within a few years, from having no innovations to repeatedly generating innovations, the authors describe important aspects of how innovative culture can be nurtured in healthcare. Data were analysed using inductive and deductive analysis steps.

Findings

The study shows that it is possible to nurture an innovative culture in a healthcare organisation. Relationships and competences beyond healthcare, empowering structures and signalling the importance of innovation work with resources all proved to be important. All are aspects that a manager can influence. In this case, the manager's role in nurturing innovative culture was very important.

Practical implications

This study highlights that an innovative culture can be nurtured in healthcare organisations and that managers can play a key role in such a process.

Originality/value

The paper describes and analyses an innovative culture in a healthcare unit and identifies important conditions and strategies for nurturing innovative culture in healthcare organisations.
The control of tax corruption: evidence from nonfungible token market in China
Authors: Rahman Jahidur , Jin Yahan
Published: February 2023

Purpose

In 2021, nonfungible token (NFT) has emerged and grown as a new digital asset and became a carrier for cryptocurrency holders in China. NFT opens the door of the digital world for creators’ rights and the realization of economic interests. However, potential problems such as money laundering, terrorist financing and tax avoidance risks have increased in China due to the lack of regulations. As tax control is an important tool used by the government to adjust the economy and market, this study aims to investigate the future market capitalization of NFT and provide value orientations to control the NFT market in China with a tax control approach based on the positive experience of other countries.

Design/methodology/approach

In this study, least squares and expert estimation are applied to predict the future market capitalization based on the global market, which can provide an understanding of the current NFT market and the significance of its tax control. In addition, the tax control and interpretation of Chinese taxation institutions and structures are also explored.

Findings

Results include the probable tax structure or policy that national institutions can carry out over different transactions. Conclusions show that introducing tax control to regulate and monitor the rise of state revenue and decline of illegal financing activities. Establishing tax control in the Chinese NFT market can provide a centralized guarantee to ensure the safety and legality of transactions and enable further progress.

Originality/value

This study puts forward new ideas on the future development of nonprofitable tokens based on blockchain technology from the perspective of taxation in China.
Occupational self-efficacy, job crafting and job satisfaction in newcomer socialization: a moderated mediation model
Authors: Yang Yingxi , Zhou Yong , Peng Siyi , Li Hairong
Published: February 2023

Purpose

Drawing on job crafting theory and the social cognitive theory of work satisfaction, the purpose of this study is to examine the impacts of task, relational and cognitive crafting on job satisfaction and how occupational self-efficacy (OSE) and hierarchical organizational culture affect the execution and outcome of job crafting behaviors.

Design/methodology/approach

Data were collected at four time points among Chinese media professionals (N = 198) during three consecutive months. Regression analysis and the bootstrap method were used for hypothesis testing.

Findings

Only cognitive crafting was found to mediate the positive relationship between OSE and job satisfaction. In a hierarchical organizational culture, the positive effects of OSE on task, relational and cognitive crafting became stronger, while the effect of task crafting on job satisfaction became negative. The authors also identified a conditional negative effect of OSE on job satisfaction via task crafting. The mediating effect of cognitive crafting was consistent despite the levels of hierarchical culture.

Practical implications

To retain new hires, organizations should look for efficacious individuals and encourage the individuals to cognitively craft individuals' jobs, especially in a hierarchical culture. Moreover, job crafting interventions should be carefully designed in this type of culture.

Originality/value

This research identifies the three dimensions of job crafting as mediators that link OSE to job satisfaction and reveals the role of hierarchical culture in moderating these relationships.
Impact of knowledge management capabilities on organisational performance in construction firms: the mediating role of innovation
Authors: Idrees Hisham , Haider Syed Arslan , Xu Jin , Tehseen Shehnaz , Jan Naveed
Published: February 2023

Purpose

This study aims to investigate the mediating effect of innovation on the relationship between KM (KM) capabilities and organisational performance in the context of construction firms operating in Pakistan. Worldwide innovation predicts the performance of any firm. Today, the construction industry in Pakistan is booming, which reinforces the need for a study on innovation and KM in this sector.

Design/methodology/approach

This empirical study uses a correlational research design. An online survey questionnaire was used as a data collection method. Through convenient sampling, the sample comprised 277 employees from different construction firms working under the Defence Housing Authority (a construction company operating in major cities) in Pakistan. Data were analysed through partial least squares-structural equation modelling (Smart PLS-SEM version 3) to assess the hypothesis.

Findings

Data analysis reveals that KM dimensions, knowledge acquisition, application and protection positively and significantly influence organisational performance; however, knowledge conversion is insignificant. Furthermore, innovation positively and substantially mediates the relationship between knowledge acquisition, application, protection, organisational performance and the insignificant terms of knowledge conversion.

Research limitations/implications

This study is limited to the construction industry, and future research should be conducted on larger scales for better generalisation. Other mediators between KM and organisational performance (i.e. organisational complexity, workplace environment, employee knowledge-sharing attitude) should be investigated.

Practical implications

These results are crucial and encourage managers in the construction industry, especially from a developing country like Pakistan, to understand the importance of innovation, the application of KM and the essential role it has in boosting business performance.

Originality/value

This research contributes to the scholarly debate on the mediating role of innovation in the relationship between KM and organisational performance. It also expands the literature on KM through an empirical investigation on the innovation of the construction industry in Pakistan from a management perspective.
Demystifying disposition effect: past, present and future
Authors: Joshipura Mayank , Joshipura Nehal , Sharma Aditya
Published: February 2023

Purpose

The disposition effect remains one of the most significant investor behavior puzzles. This study aims to consolidate the knowledge, explore current dynamics, elicit trends and offer future research directions to demystify the disposition effect.

Design/methodology/approach

This study applies the hybrid review method. It first used bibliometric analysis (212 documents), followed by content analysis (54 articles) to analyze the breadth and depth of literature on the disposition effect.

Findings

This study presents performance analysis and science mapping. It identifies five main research streams: evidence, implications and mitigation techniques; theoretical explanations; investor biases and hedonic framing; attributes, beliefs and preferences; and implications for asset pricing and market efficiency. This study further offers future research directions for disposition effect research.

Research limitations/implications

This study deploys sequential bibliometric and content analysis. A meta-analysis of quantitative articles could provide specific insights regarding the disposition effect. Besides, this study is based on Scopus-indexed journals only.

Practical implications

This study benefits investors and portfolio managers as they learn effective ways to guard against the disposition effect. Policymakers may tweak tax laws to incentivize long-term holding, and regulators can run investor education campaigns to minimize the disposition effect’s consequences effectively.

Originality/value

To the best of the authors’ knowledge, this is probably the first hybrid review of high-quality, contemporary articles on the disposition effect that offers science mapping, research streams, future research directions and a succinct summary of theories, contexts, characteristics and methods deployed in the field of research.
Natural disasters and economic policy challenges
Authors: Freebairn John
Published: February 2023

The frequency of and magnitudes of natural disasters associated with exogenous variation of climate vary between areas. Household, business and government decisions on location and investment influence the private and society costs of natural disasters. Government economic policy towards natural disasters face a challenging trade‐off between short term equity and long term efficiency objectives. Additional financial grants and subsidies for those adversely affected by a natural disaster event for equity reasons also reduce longer term private sector incentives and rewards to locate to less natural disaster‐prone areas and to invest in mitigation strategies.
Impact of state Medicaid expansion on cross‐sector health and social service networks: Evidence from a longitudinal cohort study
Authors: Hogg‐Graham Rachel , Mamaril Cezar B. , Benitez Joseph A. , Gatton Kelsey , Mays Glen P.
Published: February 2023

Objective

To examine the impact of state Medicaid expansion on the delivery of population health activities in cross‐sector health and social services networks. Community networks are multisector, interorganizational networks that provide services ranging from the direct provision of individual social services to the implementation of population‐level initiatives addressing community outcomes.

Data Sources

We used data measuring the composition of cross‐sector population health networks 2006–2018 National Longitudinal Survey of Public Health Systems (NALSYS) linked with the Area Health Resource File.

Study Design

A difference‐in‐differences approach was used to examine the impact of expansion on organization engagement in population health activities and network structure.

Data Collection/Extraction Methods

Stratified random sampling of local public health jurisdictions in the United States. We restricted our data to jurisdictions serving populations of 100,000 or more and states that had NALSYS observations across all time periods, resulting in a final sample size of 667.

Principal Findings

Results from our adjusted difference‐in‐differences estimates indicated that Medicaid expansion was associated with a 2.3 percentage point increase in the density of population health networks (p < 0.10). Communities in states that expanded Medicaid experienced significant increases in the participation of local public health, local government, hospital, nonprofit, insurer, and K‐12 schools. Of the organizations with significant increases in expansion communities, nonprofits (7.7 percentage points, p < 0.01), local public health agencies (6.5 percentage points, p < 0.01), hospitals (5.8 percentage points, p < 0.01), and local government agencies (6.0 percentage points, p < 0.05) had the largest gains.

Conclusions

Our study found increases in cross‐sector participation in population health networks in states that expanded Medicaid compared with nonexpansion states, suggesting that additional coverage gains are associated with positive changes in population health network structure.
Muslim American physicians' experiences with, and views on, religious discrimination and accommodation in academic medicine
Authors: Padela Aasim I. , Azam Laila , Murrar Sohad , Baqai Benish
Published: February 2023

Objective

To assess Muslim physician experiences with religious discrimination and identify strategies for better accommodating Muslim identity in health care.

Data Sources and Study Setting

Interviews were conducted with Muslim physicians from three US‐based Muslim clinician organizations between June and August 2021.

Study Design

In‐depth, semi‐structured qualitative interviews used a phenomenological approach to describe experiences of religious discrimination and accommodation. A team‐based framework approach to coding was used to inductively generate themes from interview data.

Data Collection/Extraction Methods

Physicians from the Islamic Medical Association of North America, American Muslim Health Professionals, and the US Muslim Physicians group were invited to participate using closed organizational listservs. Inclusion criteria sought English‐speaking, self‐identifying Muslims with current or past affiliation with a university hospital in the United States. Potential participants were segmented into groups based on responses to questions about perceived religious discrimination and accommodation. Purposive sampling was used to iteratively approach participants within these groups in order to capture a diverse respondent pool. Interviews stopped after thematic saturation was reached.

Principal Findings

Eighteen physicians (11 women and 7 men; mean age: 41.5 [standard deviation = 12.91] years) were interviewed. Nearly all (n = 16) held Islam to be important in their lives. Three overarching themes, with several subthemes, emerged. Participants (1) struggled to maintain religious practices and observances due to unaccommodating organizational structures; (2) experienced religious discrimination, which, in turn, impacted their professional trajectories and, at times, their personal well‐being; and (3) believed that institutions could implement specific educational and policy interventions to advance the religious accommodation of Muslims in health care.

Conclusions

Muslim physicians frequently encounter religious discrimination, yet there are concrete ways in which health care workplaces can better accommodate their religious needs and combat discrimination. To improve workforce diversity, equity, and inclusion, educational forums and policies that support the religious practices of physicians need to be established.
Investigation on fresh bamboo replacing rice husks for brewing light‐aroma Baijiu
Authors: Wei Yang , Zhang Li‐Qiang , Ran Mao‐Fang , Wang Song‐Tao , Yang Jian‐Gang , Shen Cai‐Hong
Published: February 2023

Husks are the main source of bran and furfural flavor in traditional Chinese light‐aroma Baijiu, but they negatively affect its smell and taste. Here, bran husks were replaced with fresh bamboo to brew light‐aroma Baijiu. Flavor components in Jiupei and Baijiu were detected through headspace solid‐phase microextraction with gas chromatography–mass spectrometry, and physicochemical properties were assessed; flavor results were obtained from correlation, principal component, and cluster analyses. Starch and reducing sugar content in Jiupei negatively correlated with moisture, alcohol content, and acidity. Fresh bamboo reduced furfural from bran husks in Jiupei by 88.5% and increased alcohol distillation by 51%; it also improved starch efficiency (5%). Surprisingly, isovanillin was found to be present in Baijiu. Total Baijiu yield (57% ± 2.01%) was attained when crushed bamboo size was 1.5 cm × 0.3 cm × 0.3 cm. This study supports the use of fresh bamboo (an eco‐friendly alternative for husks) in brewing light‐aroma Baijiu.

Practical Application

The use of fresh bamboo as a replacement for rice husks in brewing light‐aroma Baijiu was investigated. It attenuated the chaff taste in light‐aroma Baijiu and increased the liquor yield. Surprisingly, isovanillin was also present in the base Baijiu, and it added to the fragrance. This study not only supports the use of bamboo as an auxiliary material for brewing light‐aroma Baijiu but also provides a reference for brewing light‐aroma Baijiu with alternative auxiliary materials.
A CEO's expertise power and bank diversification
Authors: Ali Maisam , Gan Christopher , Nadeem Muhammad
Published: February 2023

We examine the effect of a chief executive officer (CEO)'s expertise power on bank diversification. Using US bank data from 1990 to 2020, we find that a CEO's expertise power is positively associated with bank diversification. Market competition and board composition (size and independence) positively affect this relationship. We also find that CEO delta and vega are the underlying mechanisms through which expertise power leads to greater diversification. We address endogeneity concerns using the two‐stage least squares, Heckman estimation and the difference‐in‐differences approaches and check result robustness in several ways. We provide a new explanation for bank diversification that is useful for policymakers in developing a bank strategy concerning CEO behaviour in diversification.
Does tobacco dependence worsen cannabis withdrawal in people with and without schizophrenia‐spectrum disorders?
Authors: Yeap Zac J. S. , Marsault Justine , George Tony P. , Mizrahi Romina , Rabin Rachel A.
Published: February 2023

Background and Objectives

Rates of cannabis use disorder (CUD) are higher in people with schizophrenia than in the general population. Irrespective of psychiatric diagnosis, tobacco co‐use is prevalent in those with CUD and leads to poor cannabis cessation outcomes. The cannabis withdrawal syndrome is well‐established and increases cannabis relapse risk. We investigated whether cannabis withdrawal severity differed as a function of high versus no/low tobacco dependence and psychiatric diagnosis in individuals with CUD.

Method

Men with CUD (N = 55) were parsed into four groups according to schizophrenia diagnosis and tobacco dependence severity using the Fagerstrom Test for Nicotine Dependence (FTND): men with schizophrenia with high tobacco dependence (SCT+, n = 13; FTND ≥ 5) and no/low tobacco dependence (SCT−, n = 22; FTND ≤ 4), and nonpsychiatric controls with high (CCT+, n = 7; FTND ≥ 5) and no/low (CCT−, n = 13; FTND ≤ 4) tobacco dependence. Participants completed the Marijuana Withdrawal Checklist following 12‐h of cannabis abstinence.

Results

There was a significant main effect of tobacco dependence on cannabis withdrawal severity (p < .001). Individuals with high tobacco dependence had significantly greater cannabis withdrawal severity (M = 13.85 [6.8]) compared to individuals with no/low tobacco dependence (M = 6.49, [4.9]). Psychiatric diagnosis and the interaction effects were not significant. Lastly, cannabis withdrawal severity positively correlated with FTND (r = .41, p = .002).

Conclusion and Scientific Significance

Among individuals with CUD and high tobacco dependence, cannabis withdrawal severity was elevated twofold, irrespective of diagnosis, relative to individuals with CUD and no/low tobacco dependence. Findings from this study emphasize the importance of addressing tobacco co‐use when treating CUD.
Clinical management of stage III non‐small cell lung cancer in India: An expert consensus statement
Authors: Batra Ullas , Prabhash Kumar , Agarwal Jai Prakash , Darlong Laleng , Munshi Anusheel , Penumadu Prasanth , Thangakunam Balamugesh , Bansal Abhishek
Published: February 2023

Non‐small cell lung cancer (NSCLC) is considered the most common type of lung cancer (>80% of all lung cancers); patients are often diagnosed at advanced stages of the disease. The management of NSCLC is considered challenging owing to variations in size, an extension of the tumors, involvement patterns, and classification. Although adequate literature and guidelines are available on the management of NSCLC in several countries, an Indian perspective on stage III NSCLC management is lacking. We used the modified Delphi approach to form consensus statements. A thorough literature search was done. The authors then convened and deliberated over published literature, available guidelines, and clinical judgment. Recommendation statements were formed for different clinical scenarios. These statements were sent as a form of survey to other oncologists, and their responses were recorded and mentioned. Evidence‐based statements were formed for diagnosing and managing stage III NSCLC. These recommendation statements cover various aspects—surgical, radiation, and medical treatment in various clinical scenarios including adjuvant, neoadjuvant, and consolidation therapies.
The effect of Nano‐liposomal sodium nitrite on smooth muscle cell growth in a tissue‐engineered small‐diameter vascular graft
Authors: Amoabediny Ghasem , Khakbiz Mehrdad , Jafarkhani Saeed , Mohammadi Javad , Ilanlou Shervin , Khajouei Fariba , Lotfi Leila , Rabbani Hodjattallah , Ravasjani Sonia Abbasi , Rahimi Fardin , Lee Ki‐Bum
Published: February 2023

Background

Nitric oxide is a chemical agent produced by endothelial cells in a healthy blood vessel, inhibiting the overgrowth of vascular smooth muscle cells and regulating vessel tone. Liposomes are biocompatible and biodegradable drug carriers with a similar structure to cell bilayer phospholipid membrane that can be used as useful nitric oxide carriers in vascular grafts.

Method

Using a custom‐designed apparatus, the sheep carotid arteries were decellularized while still maintaining important components of the vascular extracellular matrix (ECM), allowing them to be used as small‐diameter vascular grafts. A chemical signal of sodium nitrite was applied to control smooth muscle cells' behavior under static and dynamic cell culture conditions. The thin film hydration approach was used to create nano‐liposomes, which were then used as sodium nitrite carriers to control the drug release rate and enhance the amount of drug loaded into the liposomes.

Results

The ratio of 80:20:2 for DPPC: Cholesterol: PEG was determined as the optimum formulation of the liposome structure with high drug encapsulation efficiency (98%) and optimum drug release rate (the drug release rate was 40%, 65%, and 83% after 24, 48, and 72 h, respectively). MTT assay results showed an improvement in endothelial cell proliferation in the presence of nano‐liposomal sodium nitrite (LNS) at the concentration of 0.5 μg/mL. Using a suitable concentration of liposomal sodium nitrite (0.5 μg/mL) put onto the constructed scaffold resulted in the controllable development of smooth muscle cells in the experiment. The culture of smooth muscle cells in a pulsatile perfusion bioreactor indicated that in the presence of synthesized liposomal sodium nitrite, the overgrowth of smooth muscle cells was inhibited in dynamic cell culture conditions. The mechanical properties of ECM graft were measured, and a multi‐scale model with an accuracy of 83% was proposed to predict mechanical properties successfully.

Conclusion

The liposomal drug‐loaded small‐diameter vascular graft can prevent the overgrowth of SMCs and the formation of intimal hyperplasia in the graft. Aside from that, the effect of LNS on endothelial has the potential to stimulate endothelial cell proliferation and re‐endothelialization.
Emotional and behavioural outcomes at 8 years of age in preterm‐born children: A longitudinal study
Authors: Tsakalidis Christos , Rallis Dimitrios , Drogouti Eftychia , Kotsis Kostantinos , Kapetaniou Konstantina , Diamanti Elisavet
Published: February 2023

Aim

To evaluate the predictive value of perinatal factors and neurodevelopmental evaluation in the emotional and behavioural outcomes in preterm‐born children at 7–9 years of age.

Methods

We evaluated the Strengths and Difficulties Questionnaire (SDQ) extended score at 8.2 ± 0.2 years, among 70 preterm‐born children (32 early and 38 moderately preterms) with a previous Bayley‐III neurodevelopmental evaluation.

Results

Early compared to moderately preterms had a higher total SDQ (12 compared to 8, p = 0.031), and emotional symptoms score (4 compared to 3, p = 0.022); no significant differences were recorded in abnormal/borderline‐scored children between the two groups. The total SDQ and emotional symptoms scores were significantly correlated with gestational age, birth weight, perinatal factors and the cognitive and motor Bayley‐III scores. Early prematurity was associated with the total SDQ score (beta 2.09, 95% CI 1.32, 3.87), and the score of emotional symptoms (beta 1.70, 95% CI 1.38, 2.19), after adjusting for sex, neonatal sepsis and the existence of an older sibling.

Conclusion

Prematurity, birth weight, perinatal factors and the cognitive and motor Bayley‐III scores were significantly associated with the total SDQ and the emotional symptoms score, in preterm‐born children.
When should I run—the role of exercise timing in metabolic health
Authors: Kirchner Henriette , Weisner Leon , Wilms Britta
Published: February 2023

The prevalence of type 2 diabetes is reaching epidemic proportions. First line therapy approaches are lifestyle interventions including exercise. Although a vast amount of studies reports on beneficial effects of exercise on metabolism in humans per se, overall data are contradictory which makes it difficult to optimize interventions. Innovative exercise strategies and its underlying mechanism are needed to elucidate in order to close this therapeutic gap. The skeletal muscle produces and secretes myokines and microRNAs in response to exercise and both are discussed as mechanisms linking exercise and metabolic adaptation. Aspects of chronophysiology such as diurnal variation in insulin sensitivity or exercise as a signal to reset dysregulated peripheral clocks are of growing interest in the context of impaired metabolism. Deep insight of how exercise timing determines metabolic adaptations is required to optimize exercise interventions. This review aims to summarize the current state of research on the interaction between timing of exercise and metabolism in humans, providing insights into proposed mechanistic concepts focusing on myokines and microRNAs. First evidence points to an impact of timing of exercise on health outcome, although data are inconclusive. Underlying mechanisms remain elusive. It is currently unknown if the timed release of mykokines depends on time of day when exercise is performed. microRNAs have been found as an important mediator of processes associated with exercise adaptation. Further research is needed to evaluate their full relevance. In conclusion, it seems to be too early to provide concrete recommendations on timing of exercise to maximize beneficial effects.
Essential thrombocythemia manifesting as livedoid and purpuric skin lesions: Report of two cases and literature review
Authors: Lapeña Casado Alejandro , Santonja Carlos , García‐García Mar , Olave‐Rubio Maria Teresa , Lorda‐Espés Marta , Fink‐Puches Regina , Cerroni Lorenzo , Prieto‐Torres Lucía
Published: February 2023

Essential thrombocythemia is a chronic myeloproliferative syndrome which usually runs its course as an asymptomatic elevated platelet count. Cutaneous manifestations secondary to microcirculation abnormalities are rare but can represent a helpful diagnostic clue in order to prevent major thromboembolic events. We report two cases of heterogeneous livedoid and “net‐like” skin lesions in the context of essential thrombocythemia with identical histopathologic findings (medium‐sized blood vessels with luminal obliteration by eosinophilic material, mostly positive for the platelet marker CD61, without vasculitis). In conclusion, we seek to raise awareness of the clinicopathological features of essential thrombocythemia to allow for prompt diagnosis and treatment.
The effects of perceived network characteristics on knowledge exchange in virtual communities
Authors: Shin Seung Kyoon , Kang Kyungwoo , Sanders G. Lawrence
Published: February 2023

Understanding virtual community (VC) networks is essential because the characteristics of these networks play a fundamental role in knowledge exchange. This survey‐based study proposes two network‐related antecedents: perceived closeness with VC members (PCL) and perceived connectedness with VC members (PCN). Using a structural equation modeling approach, we examined the two antecedents' associations with the knowledge‐exchange drivers that, in turn, are related to two endogenous variables: intention to acquire knowledge and intention to share knowledge. The results of our bootstrapping mediation tests suggest that the perceived network characteristics indirectly influence members' knowledge‐exchange intentions through mediators such as identification, knowledge self‐efficacy, reputation, and shared vision. We conclude that PCN can positively influence the four mediators and is a key network characteristic that facilitates knowledge exchange in virtual spaces. By studying the antecedents of users' intentions to share and acquire knowledge, this research provides a holistic view of information exchange on VCs.
Should a benevolent government provide public goods if it cannot commit?
Authors: Silva Francisco
Published: February 2023

I compare two different systems of provision of binary public goods: a centralized system, operated by a benevolent government that has limited commitment power; and a decentralized system, based on voluntary contributions, where agents can communicate but cannot write contracts. I show that any ex‐post individually rational allocation that is implementable by the centralized system is also implementable by the decentralized system. This suggests that when the public good provision problem is merely an informational one, as is the case with binary public goods, a decentralized system may perform better.
Clinical, biological, and outcome features of P2RY8‐CRLF2 and CRLF2 over‐expression in pediatric B‐cell precursor acute lymphoblastic leukemia according to the CCLG‐ALL 2008 and 2018 protocol
Authors: Wang Ying , Li Jun , Xue Tian‐Lin , Tian Shuo , Yue Zhi‐Xia , Liu Shu‐Guang , Gao Chao
Published: February 2023

Objectives

CRLF2 alterations are associated with B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL). This study aimed to explore the clinical, biological, and outcome features of pediatric BCP‐ALL with CRLF2 abnormalities.

Methods

This study enrolled 630 childhood BCP‐ALLs treated on CCLG‐ALL 2008 or 2018 protocol. P2RY8‐CRLF2 was determined by Sanger sequencing and CRLF2 expression was evaluated by qRT‐PCR. The correlation between clinical, biological features and outcomes with P2RY8‐CRLF2 or CRLF2 over‐expression were analyzed.

Results

P2RY8‐CRLF2 and CRLF2 over‐expression were found in 3.33% and 5.71% respectively. P2RY8‐CRLF2 was associated with male, higher frequency of CD7 expression, high WBC and MRD before consolidation. CRLF2 over‐expression showed ETV6‐RUNX1−, higher frequency of CD22, CD34, CD66c, CD86 expression, hyperdiploidy and high MRD at early treatment. The lower overall survival (OS) was found in patients with P2RY8‐CRLF2 and confined only in IR group. Furthermore, adverse event‐free survival and OS of P2RY8‐CRLF2 were discovered comparing to those without known fusions or treated on CCLG‐ALL 2008 protocol. However, P2RY8‐CRLF2 was not confirmed as independent prognostic factors and no prognostic impact of CRLF2 over‐expression was found.

Conclusions

These findings indicate P2RY8‐CRLF2 identifies a subset of patients with specific features and adverse outcomes that could be improved by risk‐directed treatment.
Current and future distribution of a parasite with complex life cycle under global change scenarios: Echinococcus multilocularis in Europe
Authors: Cenni Lucia , Simoncini Andrea , Massetti Luciano , Rizzoli Annapaola , Hauffe Heidi C. , Massolo Alessandro
Published: February 2023

Global change is expected to have complex effects on the distribution and transmission patterns of zoonotic parasites. Modelling habitat suitability for parasites with complex life cycles is essential to further our understanding of how disease systems respond to environmental changes, and to make spatial predictions of their future distributions. However, the limited availability of high quality occurrence data with high spatial resolution often constrains these investigations. Using 449 reliable occurrence records for Echinococcus multilocularis from across Europe published over the last 35 years, we modelled habitat suitability for this parasite, the aetiological agent of alveolar echinococcosis, in order to describe its environmental niche, predict its current and future distribution under three global change scenarios, and quantify the probability of occurrence for each European country. Using a machine learning approach, we developed large‐scale (25 × 25 km) species distribution models based on seven sets of predictors, each set representing a distinct biological hypothesis supported by current knowledge of the autecology of the parasite. The best‐supported hypothesis included climatic, orographic and land‐use/land‐cover variables such as the temperature of the coldest quarter, forest cover, urban cover and the precipitation seasonality. Future projections suggested the appearance of highly suitable areas for E. multilocularis towards northern latitudes and in the whole Alpine region under all scenarios, while decreases in habitat suitability were predicted for central Europe. Our spatially explicit predictions of habitat suitability shed light on the complex responses of parasites to ongoing global changes.
Exploring the roles of prostanoids, leukotriens, and dietary fatty acids in cutaneous inflammatory diseases: Insights from pharmacological and genetic approaches
Authors: Honda Tetsuya , Kabashima Kenji , Kunisawa Jun
Published: February 2023

Prostanoids and leukotrienes (LTs) are representative of ω6 fatty acid‐derived metabolites that exert their actions through specific receptors on the cell surface. These lipid mediators, being unstable in vivo, act locally at their production sites; thus, their physiological functions remain unclear. However, recent pharmacological and genetic approaches using experimental murine models have provided significant insights into the roles of these lipid mediators in various pathophysiological conditions, including cutaneous inflammatory diseases. These lipid mediators act not only through signaling by themselves but also by potentiating the signaling of other chemical mediators, such as cytokines and chemokines. For instance, prostaglandin E2‐EP4 and LTB4‐BLT1 signaling on cutaneous dendritic cells substantially facilitate their chemokine‐induced migration ability into the skin and play critical roles in the priming and/or activation of antigen‐specific effector T cells in the skin. In addition to these ω6 fatty acid‐derived metabolites, various ω3 fatty acid‐derived metabolites regulate skin immune cell functions, and some exert potent anti‐inflammatory functions. Lipid mediators act as modulators of cutaneous immune responses, and manipulating the signaling from lipid mediators has the potential as a novel therapeutic approach for human skin diseases.
Optimal Treatment Regimes: A Review and Empirical Comparison
Authors: Li Zhen , Chen Jie , Laber Eric , Liu Fang , Baumgartner Richard
Published: February 2023

A treatment regime is a sequence of decision rules, one per decision point, that maps accumulated patient information to a recommended intervention. An optimal treatment regime maximises expected cumulative utility if applied to select interventions in a population of interest. As a treatment regime seeks to improve the quality of healthcare by individualising treatment, it can be viewed as an approach to formalising precision medicine. Increased interest and investment in precision medicine has led to a surge of methodological research focusing on estimation and evaluation of optimal treatment regimes from observational and/or randomised studies. These methods are becoming commonplace in biomedical research, although guidance about how to choose among existing methods in practice has been somewhat limited. The purpose of this review is to describe some of the most commonly used methods for estimation of an optimal treatment regime, and to compare these estimators in a series of simulation experiments and applications to real data. The results of these simulations along with the theoretical/methodological properties of these estimators are used to form recommendations for applied researchers.