bluuebunny/crossref_metadata_2025 huggingface dataset:
Person-Culture Personality Fit: Dispositional Traits and Cultural Context Explain Country-Level Personality Profile Conformity
Authors: Haas Brian W. , Abney Drew H. , Eriksson Kimmo , Potter Jeff , Gosling Samuel D.
Published: July 2022

In general, people are influenced by the standards set forth by groups of others; however, the levels of such conformity vary between people and across cultures. Here, we investigated factors related to country-level personality profile conformity (i.e., person-culture personality fit) across ∼5.9 million participants, residing in 57 different countries. We examined how each of the Big Five personality traits and cultural tightness are associated with variation in person-culture personality fit. We found that scoring higher in Extraversion, Agreeableness, and Conscientiousness and residing in a tight cultural context explains increased personality profile conformity, while scoring higher in Openness and Neuroticism and residing in a loose cultural context explains lower personality profile conformity. Furthermore, we found that Openness and Extraversion interact with cultural context to predict levels of personality profile conformity. These findings reveal that both dispositional and cultural factors correspond to the tendency to conform to country-level norms.
Beyond binaries? Spatial possibilities in Southeast Asia
Authors: Gillen Jamie , Bunnell Tim , Rigg Jonathan
Published: July 2022

The thoughtful and incisive responses to our article push us to address the central tension in our conceptualization of ruralization, which concerns how it both unsettles and reproduces binary thinking. On the one hand, we draw upon work in Southeast Asia that confounds binary mappings of urban versus rural space and associated divisions of labour in ways that redress the intellectual preponderance of the urban and urbanization. On the other hand, by proposing ruralization to do this, we arguably entrench a new variant of the binary (ruralization vs. urbanization). To address this tension, our response to the commentaries focuses on the ways in which they engage with the rural–urban binary. The conclusion briefly comments on the tricky pathways to theorize in step with the voices, practices, and imaginations of people in the Global South.
Body mass index, breast density, and the risk of breast cancer development in relation to the menopausal status; results from a population-based screening program in a native African-Arab country
Authors: Kamal Rasha M , Mostafa Salma , Salem Dorria , ElHatw Ahmed M , Mokhtar Sherif M , Wessam Rasha , Fakhry Sherihan
Published: July 2022

Background

Risk factors are traits or behaviors that have an influence on the development of breast cancer (BC). Awareness of the prevalent risk factors can guide in developing prevention interventions.

Purpose

To evaluate the correlation between the breast density, body mass index, and the risk of breast cancer development in relation to the menopausal status in a native African-Arab population.

Material and methods

The study included 30,443 screened females who were classified into cancer and non-cancer groups and each group was further sub-classified into pre- and postmenopausal groups. The breast density (BD) was reported and subjectively classified according to the 2013 ACR BI-RADS breast density classification. The weight and height were measured, and the body mass index (BMI) was calculated and classified according to the WHO BMI classification.

Results

A statistically significant difference was calculated between the mean BMI in the cancer and non-cancer groups ( p: .027) as well as between the pre- and postmenopausal groups ( p < .001). A positive statistically insignificant correlation was calculated between the breast density and the risk of breast cancer in the premenopausal group (OR: 1.062, p: .919) and a negative highly significant correlation was calculated in the postmenopausal group (OR: 0.234, p < .001).

Conclusion

BMI and BD are inversely associated with each other. The current studied population presented unique ethnic characteristics, where a decreased BD and an increased BMI were found to be independent risk factors for developing breast cancer.
Development of the Social Experience of a Concert Scales (SECS): The Social Experience of a Live Western Art Music Concert Influences People's Overall Enjoyment of an Event but not Their Emotional Response to the Music
Authors: O’Neill Katherine , Egermann Hauke
Published: July 2022

Social experience is often considered to be a key motivating factor for engaging with leisure activities and attendance at music concerts is no exception. Despite this, until recently, there has been limited interest in measuring the collective or social experience of live concerts in a quantitative way. Therefore, we created and validated a new measure of the social experience of a concert. In a pilot study, 103 participants were recruited across two concert settings . An extensive list of 65 items was used to measure the social experience of a concert. Based on the results, the measurement scale was reduced to 22 items.

In the main study, a further 113 participants were recruited at several concerts from a weekly series with a range of musical genres. Participants provided self-ratings of their social experience, emotional response (GEMIAC), enjoyment and demographic information in a paper survey. Based on the results of exploratory and confirmatory factor analysis we were able to reduce the number of items in the Social Experience of a Concert Scales (SECS) to 17 validated statements representing a five-factor model: Depth of Processing, Attention, Solidarity, Satisfaction, and Self-Definition. Using MANOVA, we tested the influence of these factors on the emotional response of participants to the music and found that they are not significant predictors; however, the social experience of a concert was found to be a significant predictor of enjoyment.

We have developed and validated the first quantitative measure of the social experience of a Western art music concert. Our results also suggest that the emotional response to music and the overall experience of a concert are separate and that only the latter can be influenced by the social experience of a concert.
Does Trade Facilitation Promote Export Technological Sophistication? Evidence From the European Transition Countries
Authors: Hu Yuanhong , Jiang Min , Sun Sheng , Dai Yixin
Published: July 2022

In this paper, we examine the impact of trade facilitation on the export technological sophistication from the European transition economies over 2004 to 2020. It is found that, in terms of trend, the export technological sophistication of labor-intensive and traditional resource-intensive industries is primarily concentrated in a lower range. In contrast, the export technological sophistication of capital and technology-intensive industries is generally low. Trade facilitation in each country shows a slow upward trend. The regression results show that trade facilitation significantly impacts the export technological sophistication of transition economies in general. In terms of heterogeneity, the impact is significant only in the Baltics economies, upper-middle-income and above countries, and to varying degrees in all types of light and heavy industries, differentiated industries, and technology-type industries. The mechanism analysis shows that the “reconfiguration” effect, “pushback” effect, and “spillover” effect are virtual channels through which trade facilitation affects the export technological sophistication.
Beyond Crisis? Institutionalized Mediatization of the Refugee Olympic Team at the 2020 Olympic Games
Authors: Burdsey Daniel , Michelini Enrico , Agergaard Sine
Published: July 2022

Following the global “refugee crisis” of 2015, the International Olympic Committee (IOC) established the Refugee Olympic Team (ROT), providing opportunities for refugee athletes to compete at the 2016 and 2020 (2021) Summer Olympics. To examine the changing intertwinements between wider social dynamics and mediated constructions of refugees, this article considers the IOC’s representation of the ROT around the 2020 Games. With this aim, a catalogue of articles published on the IOC’s website was examined through critical discourse analysis. Four discursive themes emerged: 1. The saving, healing and transformative power of Western sporting capital and the Olympic Games; 2. The ROT as epitome of the Global North’s inclusivity and benevolence; 3. Refugee athletes as offering hope and inspiration to other refugees; and 4. The neoliberal ideal that “hard work pays off” and “you can overcome everything” in and through sport. More broadly, current changes in the societal reception of refugees were evident in the IOC’s communication, which appeared to assume that we have moved beyond the “refugee crisis”. The IOC disseminates an “official” discourse, which elides the challenging structural conditions that refugees face after their arrival in receiving contexts, and obscures current political reluctance towards finding more long-term solutions for refugees.
Weight (Mis)perceptions and Sexual Behavior Among U.S. Emerging Adults
Authors: Ramseyer Winter Virginia , Landor Antoinette M. , Kennedy Andrea , Gillen Meghan M.
Published: July 2022

The purpose of this paper was to examine the relationship between weight misperception, age at first intercourse, and lifetime number of sex partners. We used Wave III of the National Longitudinal Study of Adolescent to Adult Health ( N = 11,522; 53.7% female), collected in 2001–2002. Results show that men who underestimate their weight have more lifetime sexual partners compared to men who accurately assess their weight. Women who underestimate their weight had fewer sexual partners and a higher age at first intercourse compared to women who accurately assess their weight. White participants who overestimated their weight had an earlier age of first intercourse, African Americans who underestimated their weight had more sexual partners, and weight misperception was not related to sexual behaviors among Hispanic and Asian participants. These findings suggest that weight underestimation’s relationship to sexual behaviors may differ by gender and race.
Does Financial Mindfulness Make a Difference? A Nexus of Financial Literacy and Behavioural Biases in Women Entrepreneurs
Authors: Iram Tahira , Bilal Ahmad Raza , Ahmad Zeshan , Latif Shahid
Published: July 2022

This article aims to determine the intervening strength of financial mindfulness between financial literacy and behavioural biases in women entrepreneurs. The literature has an enduring discussion regarding the profoundly unique financial behaviour of women. Financial literacy and behavioural biases constitute a recurrent research topic, yet how this nexus exists in the premise of women’s entrepreneurship is not well known. Building on this gap, we examined the impact of financial literacy on women entrepreneurs’ behavioural biases by focusing on financial mindfulness as a potential moderator. A random sample of 346 women entrepreneurs operating in Pakistan was analysed using structural equation modelling through AMOS 21. The results revealed a significant direct impact of financial literacy on reducing anchoring and herding bias; however, financial literacy was found to be unrelated to mental accounting bias. The moderation analysis further revealed interesting indirect impacts, such that financial literacy strongly reduced mental accounting and herding bias for financially mindful women. Nonetheless, financial mindfulness does not negatively catalyse the relationship between financial literacy and anchoring bias. By encompassing the concepts of financial literacy, mindfulness and behavioural biases, we offer a unique theoretical strand with practical implications for women entrepreneurs. We suggest new avenues for the longstanding dilemma related to the factors instigating suboptimal financial decision-making in women entrepreneurs in developing markets.
Understanding the COVID Economic Crisis: A Short- Run General Equilibrium Framework
Authors: Sarkar Agnirup
Published: July 2022

The article develops a static general equilibrium framework, in terms of which effects of the ongoing COVID-19 pandemic on output and employment of different sectors are analysed for a country like India where there are many regions, interregional migration and a large informal sector. In particular, three pandemic-induced shocks, namely, stoppage of interregional migration, supply bottlenecks and demand shrinkages are considered in a short-run set-up where prices and wages are rigid. It is shown that supply shocks in one region or sector generates binding demand constraints in others. Monetary transfer by the government increases employment and output.

JEL Classifications: D5, E2
Impact and Implementation of Plastic Surgery Interest Groups: National Survey of Plastic Surgery Interest Group Leadership
Authors: Elmer Nicholas A. , Veeramani Anamika , Hassell Natalie , Shiah Eric , Manstein Samuel , Comer Carly , Bustos Valeria , Lin Samuel J.
Published: July 2022

Background: Plastic surgery interest groups (PSIGs) provide an invaluable opportunity to enhance medical students’ exposure to and knowledge of plastic surgery. Despite this, there have been no studies that provide information on the formation of these groups as well as the aspects that make for a productive PSIG. Methods: An anonymous survey was distributed by email via RedCAP to US medical students who hold leadership positions within their medical school's PSIG. Participants were asked baseline medical school information, the structure of their interest group, and perspectives on the most impactful and challenging components of their interest group. Results: Sixteen members (27.6%) of PSIG leadership completed the survey. Eighty percent reported having a membership of greater than 20 students. Fifty percent of the PSIGs were led by advisors who were medical school or hospital-affiliated faculty. Sixty-nine percent of groups were allocated a predetermined amount of money to fund activities and events throughout the academic year. Based on member feedback, groups reported that interactions with plastic surgery faculty, mentorship opportunities, and research opportunities were the most impactful and beneficial components of their PSIG. Forty-four percent reported that the biggest challenge faced by their PSIG was having a small active member group, followed by a lack of funding. Conclusion: Our study provides an in-depth look at the current structure and impact of PSIGs in the United States. It also provides a framework for medical schools that wish to start a PSIG and suggestions for established groups who wish to revitalize their PSIG structure.
Evaluation of Temperature Changes in the Pulp Chamber During Bulk-Fill Composite Polymerization: An In-Vitro Study
Authors: Mollaoğlu Eda Yıldız , Kaptan Alper
Published: July 2022

Aim:

To investigate the temperature changes occurring in the pulp chamber during the polymerization of bulk-fill resin materials cured with different light sources by using a pulpal microcirculation simulation device in vitro.

Materials and Methods:

Class I cavities of width 2 × 3 mm were prepared on 120 permanent noncarious teeth. All samples were adjusted to maintain 2 mm dentin thickness within the pulp chamber and the cavity base. Venus Bulk Fill, Tetric Evo Ceram Bulk Fill, Filtek Bulk Fill, and Filtek Z250 were used as restorative materials. Materials were polymerized with Valo Light Emitting Diode (LED), Elipar S10, and Elipar Deepcure-S devices. A j-type thermocouple with microcirculation assemblies was used for measuring the temperature increments inside the pulp chamber during the polymerization of bulk-fill composite resins. The obtained data were recorded.

Results:

Statistically significant difference was found between the light sources and the temperature changes occurring during the polymerization ( P <.05). The difference in temperature increases was found to be significant ( P <.05) between restorative materials. The highest temperature rise values were obtained from Venus Bulk Fill.

Conclusion:

All light devices used in the study caused an increase in temperature in the pulp chamber in all groups. For all resin materials used, it was observed that the temperature values arising during the polymerization via used light sources did not exceed 5.5°C, which is the critical value for pulp.
Case of Non-Langerhans Cell Histiocytosis in a Person Living with HIV - Clinical and Therapeutic Challenge
Authors: Yancheva Nina , Strashimirov Dimitar , Dardanov Dragomir , Kamenov Bojidar , Radinoff Atanas
Published: July 2022

Non-Langerhans cell histiocytosis is a rare disease which seldom affects adults. We report a case of a 32-year-old Bulgarian woman living with HIV. She developed severe anemia, extreme splenomegaly, requiring splenectomy and vertebral tumor formations leading to fracture. The diagnosis was confirmed by histological examination of the spleen, but subsequently questioned and a cumulative disease was discussed. After genetic testing, a cumulative disease was ruled out and the condition was determined to be Non-Langerhans cell histiocytosis. According to literature data, the disease has a high mortality rate. However, in our case, we should also note that there was a delay in diagnosis by several months due to difficulties in the clarification of the hematological disorder.
Empowering leadership and team innovation: The mediating effects of team processes and team engagement
Authors: Hsu Hung-Ming , Chang Huo-Tsan , Liou Jia-Wen , Cheng Yao-Chung , Miao Min-Chih
Published: July 2022

This study explored the mediating effects of team processes and team engagement on the relationship between empowering leadership and team innovation using a time-lagged research design and two-source data, where the supervisors’ team innovation rating was measured after a 3-month lag. Structural equation modeling was used to test the hypotheses. The findings showed that (1) team processes fully mediated the positive relationship between empowering leadership and team innovation, (2) team engagement fully mediated the positive relationship between empowering leadership and team innovation, and (3) the positive covariance of both team processes and team engagement contributed to stimulating the positive effect of empowering leadership on team innovation. Theoretical implications, practical implications, and directions for future research were also discussed.
Scleromyxedema in an adult following Sinopharm BBIBP-CorV vaccination: An extremely rare phenomenon
Authors: Parsaei Amirhossein , Rezaei Somayeh Sadat , Rahmani Alireza , Masoumi Maryam , Dehghanbanadaki Hojat , Norouzi Somayyeh , Riyahi Mohammad Mehdi , Tabaraii Reihane , Montazeri Seyed Mohammad Hashem
Published: July 2022

Introduction:

The Sinopharm BBIBP-CorV vaccine produces a variety of cutaneous adverse effects. Scleromyxedema is a mucinous connective tissue disorder that causes skin thickness and sclerodermoid changes. According to our findings, this is the first case of scleromyxedema induced by the Sinopharm immunization.

Case description:

We discuss the case of a 75-year-old woman who acquired progressive thickening of the skin in her limbs and trunk after getting the Sinopharm vaccination. Examination, laboratory testing, and a biopsy were used to verify scleromyxedema diagnosis. Intravenous immunoglobulins, mycophenolate mofetil, and prednisolone were used in the treatment of the patient. The outcomes from the 4-month follow-up were reassuring.

Conclusion:

This study emphasizes the need of considering scleromyxedema as a connective tissue pathology in patients who have recently received Sinopharm vaccine and have similar cutaneous signs.
Are shifting communication styles crumbling old silos?
Authors: Miles Gayla , Quinlan Ann , Frederick Nicole , Brown Aaron
Published: July 2022

Clear communication is essential to provide high-quality health care. The medical environment is changing. Older physicians and nurses are retiring being replaced with younger professionals who are not as concerned with gender roles and who appreciate technical communication. Along with the changing setting is the introduction of communication frameworks that are more comprehensive and consider both verbal and nonverbal modems of communication. This article provides an anecdotal event evaluated by the Hannawa ‘SACCIA Safe Communication” framework but also considers the changing medical landscape which may be helping to dissolve miscommunication silos. The fast-paced, fluid medical environment calls for a more robust, interactive communication tool. Healthcare providers would benefit from education on the entire communicative process needed for successful communication.
Attitudes Toward Transgender Persons Among Medical Students of a Tertiary Health-Care Center: A Cross-Sectional Exploratory Study
Authors: Jain Harsh , Subramanian Karthick , Gowsi Keni , Sankaran Avudaiappan
Published: July 2022

Background:

Inadequate knowledge and awareness about transgenderism among doctors can lead to inadequate health-care services to transgender persons.

Objective:

To assess the prevalent attitudes and beliefs toward transgender persons amongst medical undergraduates.

Materials and Methods:

The present cross-sectional observational study included medical undergraduates of both gender in a tertiary care hospital. The students belonged to “early clinical phase” (yet to start clinical postings). The sociodemographic characteristics and academic and social exposure to transgender-related issues were recorded using a semi-structured proforma. Transgender Attitudes and Beliefs Scale was used to assess the attitudes and beliefs toward transgender persons. Statistical significance was set at P < .05.

Results:

Of the 170 second-year medical students, majority reported negligible social exposure (71.3%) and academic exposure (81.6%) to transgenderism. Female students displayed better attitudes and beliefs toward transgender persons than their male counterparts.

Conclusions:

Medical undergraduates require systematic academic exposure to transgender-related health issues. Gender differences exist among medical undergraduates in the beliefs and attitudes toward transgenderism.
Understanding Adolescent Sexuality: A Developmental Perspective
Authors: Hegde Anupama , Chandran Suhas , Pattnaik Jigyansa Ipsita
Published: July 2022

Adolescence is a period of transition from childhood to adulthood, during which the individual undergoes significant biological, psychological, and social changes. The development of sexuality, though begins at conception, gets shaped during this period. The changes occurring differ in males and females not just in terms of biopsychosocial organization but sexual behavior and functioning as well. Adolescent sexuality is although highly acknowledged but is quite complex and needs in-depth understanding. Challenges faced by adolescents include being vulnerable to risky sexual behaviors, unprotected sex, nonconsensual sexual interactions, sexually transmitted infections, stigmatization from society, and so on. In developing countries such as India, adolescents deal with additional challenges with higher risk associated with early marriages, unplanned pregnancies, sexual abuse, patriarchy, and insufficient information regarding sexual behavior and risks. This article is an attempt to review the nuances of adolescent sexuality, particularly in developing countries, to ensure appropriate culturally sensitive yet scientifically sound intervention programs.
Psychosexual Advantages of Physical Adaptation
Authors: Kar Sujita Kumar , Singh Garima
Published: July 2022

Physical adaptation is a process by which an organism attempts to adjust successfully with the changes happening in the environment continuously. Organisms adapting effectively in this process have an advantage of long survivability. During the process of evolution, several physical (structural) changes happened in humans that gives them a reproductive advantage. This article discusses the specific physical adaptations that gives psychosexual advantages in human.
A Conceptual Framework for Enabling Risk in Inclusive Postsecondary Education Programs
Authors: Rooney-Kron Magen , Regester April , Lidgus Jonathan , Worth Christopher , Bumble Jennifer L. , Athamanah Lindsay S.
Published: July 2022

More students with intellectual and developmental disability (IDD) are attending post-secondary education than ever before. As more students with IDD enter college, inclusive post-secondary education programs (IPSE) will be required to make important decisions about the types of services and supports they provide. IPSE program staff should aim to provide supports and services that honor students’ dignity of risk and facilitate opportunities for students to take risks. The purpose of this article is to describe a conceptual framework IPSE program staff can use to assess the extent to which the supports and services they provide enable risk-taking opportunities for students in their program. The framework includes five steps: identify areas for growth, understand risks and rewards for students and stakeholders, evaluate natural supports and determine appropriate supplemental supports, identify and enable access to natural consequences, and reflect and plan for more authentic risk. An example of how to use the framework in the context of residential housing will be described.
Nationwide Analysis of Complex Midface Advancement in Pediatric Patients
Authors: Kalmar Christopher L. , O’Sick Nicholas R. , Pontell Matthew E. , Golinko Michael S.
Published: July 2022

Background:

The purpose of this study was to utilize a multicenter database to better understand preexisting comorbidities, postoperative complications, and hospital financial charges for pediatric patients undergoing complex midface advancement procedures.

Methods:

Retrospective cohort study was conducted of patients undergoing midface advancement, including Le Fort II (LF2), Le Fort III (LF3), and Monobloc procedures in the United States between 2010 and 2020 using the Pediatric Health Information System. Preexisting comorbidities, postoperative complications, and hospital admission charges among these cohorts were analyzed.

Results:

During the study interval, 91 patients underwent complex midface reconstruction. Median age was 12.7 years. Postoperative complication rate was 44.0%, and LF2 procedures had fewer surgical complications than LF3 ( P < .001) and Monobloc ( P < .001). Distraction osteogenesis was utilized in 29.7% of midface advancement procedures. LF2 procedures were less likely to require blood transfusions than LF3 ( P < .001) and Monobloc ( P < .001). Hospital admission charges tripled over the last 10 years ( P = .004), and these charges varied significantly across regions of the country ( P < .001). Patients undergoing LF2 had lower hospital admission charges than those undergoing LF3 ( P < .001) and Monobloc ( P < .001). Several patients (30.3%) chose a farther hospital than the one locally available.

Conclusions:

While midface advancement procedures are conceptually grouped together, LF2 has significantly lower surgical complications, blood transfusions, hospital lengths of stay, hospital admission charges, ICU lengths of stay, and ICU charges than LF3 or Monobloc procedures.
Genetic testing in severe aplastic anemia is required for optimal hematopoietic cell transplant outcomes
Authors: McReynolds Lisa J. , Rafati Maryam , Wang Youjin , Ballew Bari J. , Kim Jung , Williams Valencia V. , Zhou Weiyin , Hendricks Rachel M. , Dagnall Casey , Freedman Neal D. , Carter Brian , Strollo Sara , Hicks Belynda , Zhu Bin , Jones Kristine , Paczesny Sophie , Marsh Steven G. E. , Spellman Stephen R. , He Meilun , Wang Tao , Lee Stephanie J. , Savage Sharon A. , Gadalla Shahinaz M.
Published: July 2022

Patients with severe aplastic anemia (SAA) can have an unrecognized inherited bone marrow failure syndrome (IBMFS) because of phenotypic heterogeneity. We curated germline genetic variants in 104 IBMFS-associated genes from exome sequencing performed on 732 patients who underwent hematopoietic cell transplant (HCT) between 1989 and 2015 for acquired SAA. Patients with pathogenic or likely pathogenic (P/LP) variants fitting known disease zygosity patterns were deemed unrecognized IBMFS. Carriers were defined as patients with a single P/LP variant in an autosomal recessive gene or females with an X-linked recessive P/LP variant. Cox proportional hazard models were used for survival analysis with follow-up until 2017. We identified 113 P/LP single-nucleotide variants or small insertions/deletions and 10 copy number variants across 42 genes in 121 patients. Ninety-one patients had 105 in silico predicted deleterious variants of uncertain significance (dVUS). Forty-eight patients (6.6%) had an unrecognized IBMFS (33% adults), and 73 (10%) were carriers. No survival difference between dVUS and acquired SAA was noted. Compared with acquired SAA (no P/LP variants), patients with unrecognized IBMFS, but not carriers, had worse survival after HCT (IBMFS hazard ratio [HR], 2.13; 95% confidence interval[CI], 1.40-3.24; P = .0004; carriers HR, 0.96; 95% CI, 0.62-1.50; P = .86). Results were similar in analyses restricted to patients receiving reduced-intensity conditioning (n = 448; HR IBMFS = 2.39; P = .01). The excess mortality risk in unrecognized IBMFS attributed to death from organ failure (HR = 4.88; P < .0001). Genetic testing should be part of the diagnostic evaluation for all patients with SAA to tailor therapeutic regimens. Carriers of a pathogenic variant in an IBMFS gene can follow HCT regimens for acquired SAA.
Towards an artificial human lung: modelling organ-like complexity to aid mechanistic understanding
Authors: Humbert Maria Victoria , Spalluto Cosma Mirella , Bell Joseph , Blume Cornelia , Conforti Franco , Davies Elizabeth R. , Dean Lareb S.N. , Elkington Paul , Haitchi Hans Michael , Jackson Claire , Jones Mark G. , Loxham Matthew , Lucas Jane S. , Morgan Hywel , Polak Marta , Staples Karl J. , Swindle Emily J. , Tezera Liku , Watson Alastair , Wilkinson Tom M.A.
Published: July 2022

Respiratory diseases account for over 5 million deaths yearly and are a huge burden to healthcare systems worldwide. Murine models have been of paramount importance to decode human lung biologyin vivo, but their genetic, anatomical, physiological and immunological differences with humans significantly hamper successful translation of research into clinical practice. Thus, to clearly understand human lung physiology, development, homeostasis and mechanistic dysregulation that may lead to disease, it is essential to develop models that accurately recreate the extraordinary complexity of the human pulmonary architecture and biology. Recent advances in micro-engineering technology and tissue engineering have allowed the development of more sophisticated models intending to bridge the gap between the native lung and its replicatesin vitro. Alongside advanced culture techniques, remarkable technological growth in downstream analyses has significantly increased the predictive power of human biology-basedin vitromodels by allowing capture and quantification of complex signals. Refined integrated multi-omics readouts could lead to an acceleration of the translational pipeline fromin vitroexperimental settings to drug development and clinical testing in the future. This review highlights the range and complexity of state-of-the-art lung models for different areas of the respiratory system, from nasal to large airways, small airways and alveoli, with consideration of various aspects of disease states and their potential applications, including pre-clinical drug testing. We explore how development of optimised physiologically relevantin vitrohuman lung models could accelerate the identification of novel therapeutics with increased potential to translate successfully from the bench to the patient's bedside.
Benefits of specialist severe asthma management: demographic and geographic disparities
Authors: Redmond Charlene , Heaney Liam G. , Chaudhuri Rekha , Jackson David J. , Menzies-Gow Andrew , Pfeffer Paul , Busby John
Published: July 2022

Background

The benefits of specialist assessment and management have yet to be evaluated within the biologic era of UK severe asthma treatment, and potential disparities have not been considered.

Methods

In an uncontrolled before-and-after study, we compared asthma symptoms (Asthma Control Questionnaire-6 (ACQ-6)), exacerbations, unscheduled secondary care use, lung function (forced expiratory volume in 1 s (FEV1)) and oral corticosteroid (OCS) dose after 1 year. We compared outcomes by sex, age (18–34, 35–49, 50–64 and ≥65 years), ethnicity (Caucasianversusnon-Caucasian) and hospital site after adjusting for demographics and variation in biologic therapy use.

Results

1140 patients were followed-up for 1370 person-years from 12 specialist centres. At annual review, ACQ-6 score was reduced by a median (interquartile range (IQR)) of 0.7 (0.0–1.5), exacerbations by 75% (33–100%) and unscheduled secondary care by 100% (67–100%). FEV1increased by a median (IQR) of 20 (−200–340) mL, while OCS dose decreased for 67% of patients. Clinically meaningful improvements occurred across almost all patients, including those not receiving biologic therapy. There was little evidence of differences across demographic groups, although those aged ≥65 years demonstrated larger reductions in exacerbations (69%versus52%; p<0.001) and unscheduled care use (77%versus50%; p<0.001) compared with patients aged 18–34 years. There were >2-fold differences between the best and worst performing centres across all study outcomes.

Conclusions

Specialist assessment and management is associated with substantially improved patient outcomes, which are broadly consistent across demographic groups and are not restricted to those receiving biologic therapy. Significant variation exists between hospitals, which requires further investigation.
Adverse roles of mast cell chymase-1 in COPD
Authors: Liu Gang , Jarnicki Andrew G. , Paudel Keshav R. , Lu Wenying , Wadhwa Ridhima , Philp Ashleigh M. , Van Eeckhoutte Hannelore , Marshall Jacqueline E. , Malyla Vamshikrishna , Katsifis Angelica , Fricker Michael , Hansbro Nicole G. , Dua Kamal , Kermani Nazanin Z. , Eapen Mathew S. , Tiotiu Angelica , Chung K. Fan , Caramori Gaetano , Bracke Ken , Adcock Ian M. , Sohal Sukhwinder S. , Wark Peter A. , Oliver Brian G. , Hansbro Philip M.
Published: July 2022

Background

COPD is the third leading cause of death worldwide. Cigarette smoke (CS)-induced chronic inflammation inducing airway remodelling, emphysema and impaired lung function is the primary cause. Effective therapies are urgently needed. Human chymase (hCMA)1 and its orthologue mCMA1/mouse mast cell protease (mMCP)5 are exocytosed from activated mast cells and have adverse roles in numerous disorders, but their role in COPD is unknown.

Methods

We evaluated hCMA1 levels in lung tissues of COPD patients. We usedmmcp5-deficient (−/−) mice to evaluate this protease's role and potential for therapeutic targeting in CS-induced experimental COPD. In addition, we usedex vivo/in vitrostudies to define mechanisms.

Results

The levels of hCMA1 mRNA and CMA1+mast cells were increased in lung tissues from severe compared to early/mild COPD patients, non-COPD smokers and healthy controls. Degranulated mast cell numbers and mMCP5 protein were increased in lung tissues of wild-type mice with experimental COPD.mmcp5−/−mice were protected against CS-induced inflammation and macrophage accumulation, airway remodelling, emphysema and impaired lung function in experimental COPD. CS extract challenge of co-cultures of mast cells from wild-type, but notmmcp5−/−mice with wild-type lung macrophages increased in tumour necrosis factor (TNF)-α release. It also caused the release of CMA1 from human mast cells, and recombinant hCMA-1 induced TNF-α release from human macrophages. Treatment with CMA1 inhibitor potently suppressed these hallmark features of experimental COPD.

Conclusion

CMA1/mMCP5 promotes the pathogenesis of COPD, in part, by inducing TNF-α expression and release from lung macrophages. Inhibiting hCMA1 may be a novel treatment for COPD.
Bone morphogenetic protein 4 inhibits pulmonary fibrosis by modulating cellular senescence and mitophagy in lung fibroblasts
Authors: Guan Ruijuan , Yuan Liang , Li Jingpei , Wang Jian , Li Ziying , Cai Zhou , Guo Hua , Fang Yaowei , Lin Ran , Liu Wei , Wang Lan , Zheng Qiuyu , Xu Jingyi , Zhou You , Qian Jing , Ding Mingjing , Luo Jieping , Li Yuanyuan , Yang Kai , Sun Dejun , Yao Hongwei , He Jianxing , Lu Wenju
Published: July 2022

Background

Accumulation of myofibroblasts is critical to fibrogenesis in idiopathic pulmonary fibrosis (IPF). Senescence and insufficient mitophagy in fibroblasts contribute to their differentiation into myofibroblasts, thereby promoting the development of lung fibrosis. Bone morphogenetic protein 4 (BMP4), a multifunctional growth factor, is essential for the early stage of lung development; however, the role of BMP4 in modulating lung fibrosis remains unknown.

Methods

The aim of this study was to evaluate the role of BMP4 in lung fibrosis using BMP4-haplodeleted mice, BMP4-overexpressed mice, primary lung fibroblasts and lung samples from patients with IPF.

Results

BMP4 expression was downregulated in IPF lungs and fibroblasts compared to control individuals, negatively correlated with fibrotic genes, and BMP4 decreased with transforming growth factor (TGF)-β1 stimulation in lung fibroblasts in a time- and dose-dependent manner. In mice challenged with bleomycin, BMP4 haploinsufficiency perpetuated activation of lung myofibroblasts and caused accelerated lung function decline, severe fibrosis and mortality. BMP4 overexpression using adeno-associated virus 9 vectors showed preventative and therapeutic efficacy against lung fibrosis.In vitro, BMP4 attenuated TGF-β1-induced fibroblast-to-myofibroblast differentiation and extracellular matrix (ECM) production by reducing impaired mitophagy and cellular senescence in lung fibroblasts. Pink1 silencing by short-hairpin RNA transfection abolished the ability of BMP4 to reverse the TGF-β1-induced myofibroblast differentiation and ECM production, indicating dependence on Pink1-mediated mitophagy. Moreover, the inhibitory effect of BMP4 on fibroblast activation and differentiation was accompanied with an activation of Smad1/5/9 signalling and suppression of TGF-β1-mediated Smad2/3 signallingin vivoandin vitro.

Conclusion

Strategies for enhancing BMP4 signalling may represent an effective treatment for pulmonary fibrosis.
Associations of hiatus hernia with CT-based interstitial lung changes: the MESA Lung Study
Authors: Kim John S. , Kim Jinhye , Yin Xiaorui , Hiura Grant T. , Anderson Michaela R. , Hoffman Eric A. , Raghu Ganesh , Noth Imre , Manichaikul Ani , Rich Stephen S. , Smith Benjamin M. , Podolanczuk Anna J. , Garcia Christine Kim , Barr R. Graham , Prince Martin R. , Oelsner Elizabeth C.
Published: July 2022

Background

Hiatus hernia (HH) is prevalent in adults with pulmonary fibrosis. We hypothesised that HH would be associated with markers of lung inflammation and fibrosis among community-dwelling adults and stronger amongMUC5B(rs35705950) risk allele carriers.

Methods

In the Multi-Ethnic Study of Atherosclerosis, HH was assessed from cardiac and full-lung computed tomography (CT) scans performed at Exam 1 (2000–2002, n=3342) and Exam 5 (2010–2012, n=3091), respectively. Percentage of high attenuation areas (HAAs; percentage of voxels with attenuation between −600 and −250 HU) was measured from cardiac and lung scans. Interstitial lung abnormalities (ILAs) were examined from Exam 5 scans (n=2380). Regression models were used to examine the associations of HH with HAAs, ILAs and serum matrix metalloproteinase-7 (MMP-7), and adjusted for age, sex, race/ethnicity, educational attainment, smoking, height, weight and scanner parameters for HAA analysis.

Results

HH detected from Exam 5 scans was associated with a mean percentage difference in HAAs of 2.23% (95% CI 0.57–3.93%) and an increase of 0.48% (95% CI 0.07–0.89%) per year, particularly inMUC5Brisk allele carriers (p-value for interaction=0.02). HH was associated with ILAs among those <80 years of age (OR for ILAs 1.78, 95% CI 1.14–2.80) and higher serum MMP-7 level among smokers (p-value for smoking interaction=0.04).

Conclusions

HH was associated with more HAAs over time, particularly amongMUC5Brisk allele carriers, and ILAs in younger adults, and may be a risk factor in the early stages of interstitial lung disease.
An observational study to determine the relationship between cough frequency and markers of inflammation in severe asthma
Authors: Holmes Joshua , McGarvey Lorcan P.A. , Birring Surinder S. , Fletcher Hannah , Heaney Liam G.
Published: July 2022

Background

The relationship between objectively measured cough and type 2 (T2) biomarkers and other measures of asthma control and severity is poorly understood. The objective of this study was to assess the relationship between objective and subjective cough measurement tools and clinical biomarkers of asthma.

Methods

Patients with severe asthma and mild-to-moderate asthma completed validated asthma and cough-related measurement tools (including ambulatory cough monitoring) and measurement of spirometry and T2 biomarkers (exhaled nitric oxide fraction (FENO) and peripheral blood eosinophil count). Patients were classified according to T2 status based on T2-low (FENO<20 ppb and peripheral blood eosinophils <150 cells·µL−1), T2-intermediate (FENO≥20 ppb or peripheral blood eosinophils ≥150 cells·µL−1) or T2-high (FENO≥20 ppb and peripheral blood eosinophils ≥150 cells·µL−1).

Results

61 patients completed the study measurements (42 severe asthma and 19 mild-to-moderate asthma). Patients with severe asthma had higher rates of cough than those with mild-to-moderate asthma in terms of total 24-h cough counts (geometric mean±sd170.3±2.7versus60.8±4.1; p=0.002) and cough frequency (geometric mean±sd7.1±2.7versus2.5±4.1 coughs·h−1; p=0.002). T2-low patients with severe asthma had significantly lower 24-h cough frequency compared with T2-intermediate and T2-high patients.

Conclusions

In patients with low biomarkers of T2 inflammation, cough frequency measurements were not elevated, suggesting that the mechanism for cough in asthma is underlying T2 eosinophilic inflammation and the logical first step for treating cough in asthma may be to achieve adequate suppression of T2 inflammation with currently available therapies.
The headache registry of the German Migraine and Headache Society (DMKG): baseline data of the first 1,351 patients
Authors: Ruscheweyh Ruth , Klonowski Theresa , Goßrau Gudrun , Kraya Torsten , Gaul Charly , Straube Andreas , Jürgens Tim Patrick , Scheidt Jörg , Förderreuther Stefanie
Published: July 2022

Background

Although good treatment options exist for many headache disorders, not all patients benefit and disability continues to be large. To design strategies for improving headache care, real-world data observing standard care is necessary. Therefore, the German Migraine and Headache Society (DMKG) has established the DMKG Headache Registry. Here we present methods and baseline data.

Methods

Accredited German headache centers (clinic-based or private practice) can offer participation to their patients. Patients provide headache history, current headache load (including a mobile headache diary), medication and comorbidities and answer validated questionnaires, prior to their physician appointment. Physicians use these data as the base of their history taking, and add, change or confirm some central information. Before the next visit, patients are asked to update their data. Patients will continuously be included over the next years.

Results

The present analysis is based on the first 1,351 patients (1110 females, 39.6 ± 12.9 years) with a completed first visit. Most participants had a migraine diagnosis. Participants had 14.4 ± 8.5 headache days and 7.7 ± 6.1 acute medication days per month and 63.9% had a migraine disability assessment (MIDAS) grade 4 (severe disability). 93.6% used at least one acute headache medication, most frequently a triptan (60.0%) or non-opioid analgesic (58.3%). 45.0% used at least one headache preventive medication, most frequently an antidepressant (11.4%, mostly amitriptyline 8.4%) or a CGRP(receptor) antibody (9.8%). Most common causes for discontinuation of preventive medication were lack of effect (54.2%) and side effects (43.3%).

Conclusion

The DMKG Headache Registry allows to continuously monitor headache care at German headache centers in both a cross-sectional and a longitudinal approach.

Trial registration

The DMKG Headache Registry is registered with the German Clinical Trials Register (DRKS00021081).
An assessment of requirements in investments, new technologies, and infrastructures to achieve the SDGs
Authors: Leal Filho Walter , Vidal Diogo Guedes , Chen Chen , Petrova Maria , Dinis Maria Alzira Pimenta , Yang Peter , Rogers Steven , Álvarez-Castañón Lorena , Djekic Ilija , Sharifi Ayyoob , Neiva Samara
Published: July 2022

Background

The implementation of the Sustainable Development Goals (SDGs) requires much planning and the provision of resources, especially regarding the necessary investments, technologies and infrastructures needed. Yet, it is presently unclear how available these elements are, what gaps exist, what changes have taken place in terms of their availability since the adoption of the SDGs and what their requirements will be in the future. The knowledge gap has become even more concerning because of the impact of the COVID-19 pandemic. Using a bibliometric analysis, an assessment of the global progress of SDG implementation and requirements, identifying challenges through the development of a matrix, and a set of 11 case studies to triangulate the holistic analysis, an assessment of the global progress of the SDGs implementation and the impact of the COVID-19 pandemic on this process was carried out.

Results

The findings suggest that the scope and width of resources limitation are currently undermining the implementation of the SDGs. Apart from the fact that the pace of progress has been insufficient, the potential of the SDGs in pursuing sustainability and improving life quality is not fully realised. This trend suggests that a substantial acceleration of the efforts is needed, especially for the five SDGs whose progress since 2015 has not been optimal, namely SDG2, SDG11, SDG13, SDG15, and SDG16, while SDG3, SDG7, SDG9, SDG14, and SDG17 show signs of progress. The case studies showed that different industries have dissimilar effects on achieving the SDGs, with the food sector correlating with 15 SDGs, as opposed to the energy sector correlating with 6 SDGs. Accordingly, the priority level assessment in terms of achieving the SDGs, points to the need to further advance the above-mentioned five SDGs, i.e., 2, 11, 13, 15 and 16.

Conclusions

This study fills in a knowledge gap in respect of the current need for and availability of investments, new technologies, and infrastructures to allow countries to pursue the SDGs. It is suggested that this availability is rather limited in specific contexts. In respect of the needs to be addressed, these include resource-related constraints, limited technologies and infrastructures, affecting SDG2, SDG11, SDG13, SDG15, and SDG16, whose progress needs to be enhanced. Since the global progress in the process of implementation of the SDGs depends directly and indirectly on addressing the resource gaps, it is suggested that this topic be further investigated, so that the present imbalances in the three dimensions of sustainable development: the economic, social and environmental, be adequately addressed.