bluuebunny/crossref_metadata_2025 huggingface dataset:
Revealing the Acetylcholinesterase Inhibitory Potential of Phyllanthus amarus and Its Phytoconstituents: In Vitro and in Silico Approach
Authors: Faloye Kolade O , Mahmud Shafi , Fakola Emmanuel G , Oyetunde Yemisi M , Fajobi Sunday J , Ugwo Jeremiah P , Olusola Ayobami J , Famuyiwa Samson O , Olajubutu Oluwabukunmi G , Oguntade Temitope I , Obaidullah Ahmad J
Published: August 2022

The inhibition of acetylcholinesterase plays a vital role in the treatment of Alzheimer disease. This study aimed to explore the acetylcholinesterase inhibition potential of Phyllanthus amarus and its phytoconstituents through an in vitro and in silico approach. The in vitro acetylcholinesterase inhibitory activity of P amarus was carried out, followed by the molecular docking studies of its phytoconstituents. The top-ranked molecules identified through molecular docking were subjected to molecular dynamics simulation (MDS) and density functional theory (DFT) studies. The results obtained revealed the methanolic extract of P amarus as a potent acetylcholinesterase inhibitor, while amarosterol A, hinokinin, β-sitosterol, stigmasterol and ellagic acid were identified as potential acetylcholinesterase inhibitors. The MDS and DFT results are in agreement with those obtained from the docking studies. Our findings suggest further studies on the hit molecules.
Friction and wear improvement by using Curcumin as a natural additive in green lubricants
Authors: Hernández-Sierra María Teresa , Báez José E , Aguilera-Camacho Luis Daniel , García-Miranda J Santos , Moreno Karla J
Published: August 2022

Lubrication is an essential mechanism to make machines and engines more efficient by lowering friction and wear. Despite this, to mitigate environmental damage, lubricants must come from renewable sources and be biodegradables. Therefore, this study analyzed the use of Curcumin as a natural additive in two green oils to improve their tribological and oxidative performance. The density and viscosity of lubricants with and without curcumin additive, as well as the lubrication regime, were determined. The operational performance was analyzed by tribological tests under a ball-on-disk configuration at 100°C based on the ASTM G99. The oxidative behavior of lubricants was examined by studying the IR bands for primary and secondary oxidative products, as well as by DSC-TGA techniques for evaluating the Oxidation Onset Temperature and the thermogravimetric behavior. At the studied conditions, the incorporation of Curcumin into the oils increased the viscosity of the lubricants up to 46%, the friction coefficient decreased up to 70%, and wear was diminished up to 96%, despite working in boundary lubrication. Moreover, the addition of curcumin noticeably enhanced the oxidation behavior of lubricants. The results of this research suggest that Curcumin is an excellent option to improve the physical properties, operational performance, and oxidative stability of green oils to create effective and environmentally friendly lubricants.
Impact of Japanese travelers’ psychographics on domestic travel intention during the COVID-19 pandemic
Authors: Handler Isabell , Tan Caroline S. L
Published: August 2022

To develop tourism products and campaigns that will not only help the tourism industry to survive, but also revive and sustain it in the future, it is imperative to understand the behavioral intentions of leisure travelers during the coronavirus disease (COVID-19) pandemic. This study aims to explore how Japanese traveler segments are characterized by their attitudes and feelings toward domestic travel during the COVID-19 pandemic. A market research study was conducted on Japanese nationals, using 1353 questionnaires in the analysis. A factor analysis was generated in six attitude dimensions: 1) COVID-19 Anxiety, 2) Government Mistrust, 3) Psychological Impact, 4) Optimistic Outlook, 5) Financial Impact, and 6) Social Anxiety; through K-means cluster analysis, the segmentation produced three distinct tourist segments: Confident Travelers, Anxious Travelers, and Social Travelers. Each segment is clearly described in terms of attitudes, considering distinct socio-demographic characteristics. Practical suggestions on how to manage and target these segments include implementing travel packages with minimal face-to-face contact for anxious travelers, travel subsidies through national campaigns for confident travelers, or conventional marketing campaigns for social travelers.
‘Welcome to a Coronavirus production’: Beyond Bows and Arrows’ Indigenous on-air community-building during lockdown
Authors: Moylan Katie
Published: August 2022

This article examines intertribal community-building in Indigenous-produced radio show Beyond Bows and Arrows, broadcast since 1983 in Dallas, Texas, and explores ways in which on-air Indigenous articulations function as acts of resurgence in turn reinforcing an Indigenous internationalism. In this critical exploration, I draw on Beyond Bows and Arrows ( BBAA) content broadcast between April and June 2020. I analyse components of the radio sound text such as in-studio talk; discussion topics; music selection and verbal segues; and station-produced informational Public Service Announcements (PSAs); and identify recurring preoccupations over three months of weekly programming during the pandemic's first lockdown. In particular, I consider BBAA's foregrounding of pandemic protocols, calls for Census 2020 participation and Black Lives Matter solidarity at the start of the unsettled yet generative 2020 summer and examine how these articulations coalesce into an on-air structure of feeling which in turn embodies the show's ongoing decolonizing project.
Loneliness, subjective health complaints, and medicine use among Finnish adolescents 2006–2018
Authors: Lyyra Nelli , Junttila Niina , Tynjälä Jorma , Villberg Jari , Välimaa Raili
Published: August 2022

Aims:

Loneliness is an important public health challenge for all ages. This study reports time trends of loneliness among adolescents over a 12-year period and analyses the strength of the associations between loneliness, health complaints, and medicine use.

Methods:

Data were derived from the cross-sectional Finnish Health Behaviour in School-aged Children study conducted in 2006, 2010, 2014, and 2018. The study population is based on a random sample of schools with 20,444 participants aged 11–15 years. The trends were analysed with a Mantel–Haenszel test, and the strength of the associations was evaluated by mixed-effects logistic and linear regressions.

Results:

An increasing prevalence in frequent loneliness (2006: 11%; 2018: 15%) was evident over the 12-year study period, especially in girls and 15-year-olds. Among all adolescents, loneliness was associated with a higher risk of recurrent health complaints and medicine use to treat the corresponding health issues, especially nervousness (odds ratio 5.8) and sleeping difficulties (odds ratio 7.6).

Conclusions:

Adolescence is a period of higher risk of frequent loneliness and associated health complaints. In this study, loneliness was common among adolescence and an increasing trend of loneliness was observed between 2006 and 2018. Also, psychosomatic health complaints and medicine use were strongly associated with loneliness. Persistent loneliness is a significant health risk and failure to resolve loneliness before entering adulthood may imply significant concerns for future well-being.
Cervical cancer (over-)screening in Europe: Balancing organised and opportunistic programmes
Authors: De Prez Vincent , Jolidon Vladimir , Cullati Stéphane , Burton-Jeangros Claudine , Bracke Piet
Published: August 2022

Aims:

Cervical cancer (CC) over-screening has been understudied in Europe, yet is relevant for approaching inequalities in screening uptake. Focusing on countries’ screening strategies (opportunistic systems versus organised programmes), we assess in which contexts CC over-screening is more prevalent, and which women are more likely to have engaged in cervical cancer screening (CCS) within the past year.

Methods:

A two-level (multilevel) design among screening women ( N = 80,761) nested in 31 European countries was used to analyse data from the second wave (2013–2015) of the European Health Interview Survey. We focused on over-screening, defined as screening more frequently than the three-yearly screening interval prescribed in the European guidelines – that is, having screened within the past year.

Results:

Higher levels of over-screening were observed in opportunistic systems compared to systems with organised programmes. In opportunistic systems, women with a higher socioeconomic position had a higher likelihood of being screened within the past year than their socioeconomic counterparts. Moreover, these differences diminished under organised programmes.

Conclusions:

Contexts with organised CCS programmes are more efficiently reducing over-screening, and enforcing the European guidelines. We suggest that the physician–patient relationship is an essential pathway for explaining socioeconomic differences in CC (over-)screening and for future interventions.
Job satisfaction and job tenure of people with mental health disorders: a UK Biobank cohort study
Authors: Mohammad Salahuddin , Miguet Maud , Rukh Gull , Schiöth Helgi B. , Mwinyi Jessica
Published: August 2022

Aims:

Job satisfaction plays an important role for the life quality and health of working individuals. While studies have shown that self-reported mental health conditions such as stress, anxiety and depression are associated with job satisfaction, a large population-based study exploring and comparing self-reported physician posed diagnosed conditions and their association with job satisfaction and job tenure is missing. This study addresses the gap along with exploring the impact of the neurotic personality trait and other possible contributing factors.

Methods:

Sixteen mental health disorders diagnosed by physicians, categorised into four major groups were investigated in relation to employment status (108,711 participants) and in relation to job satisfaction and job tenure (34,808 participants). Analyses were performed using linear regression adjusted for age, sex, townsend deprivation index, body mass index, education, physical activity, work hours and neuroticism.

Results:

Neurotic and stress disorders, eating disorders and other mental health disorders were strongly associated with lower job satisfaction and shorter job tenure in both unadjusted and adjusted analyses. Neuroticism was strongly linked to job satisfaction but was not associated with job tenure.

Conclusions:

Study findings clarify the complex relationship of mental health with job satisfaction and job tenure, which is very important to understand in designing measures to improve working life participation of individuals with mental health issues.
From heroism to martyrdom: Entrepreneurial identity work in alternative market movements
Authors: Mars Matthew M.
Published: August 2022

Entrepreneurs play a critical role in the implementation of alternative market movement agendas. The courage and sacrifices of prosocial entrepreneurs who break from the mainstream in support of collective causes are often heroized. In the current study, I use a multiple case study design to explore the heroization of localized food entrepreneurs (LFEs) who are rigidly aligned with the local food movement. I am particularly attentive to how such heroization occurs through a combination of public narratives and the identity work of the entrepreneurs themselves. I argue that heroization reinforces and sustains the rigid alignment between the LFEs and the local food movement and in doing so insidiously compromises their livelihoods and the transformative capacities of their enterprises and the movement as a whole. I draw on the insights generated to introduce to marketing theory the concept of entrepreneurial martyrdom.
Phenomenology of anxiety in people living with mild to moderate dementia: A conceptual meta-ethnographic review
Authors: Pacas Fronza Gabriela , Liddle Jacki , Mitchell Leander K. , Byrne Gerard J. , Pachana Nancy A. , Dissanayaka Nadeeka N.
Published: August 2022

Objectives

This conceptual review aims to integrate findings from published qualitative studies focusing on individual experiences of people living with dementia to generate a better understanding and conceptualisation of anxiety in dementia, including its subclinical manifestations. The review aims to inform the clinical practice to facilitate the development of targeted psychological interventions and provision of holistic support to people living with dementia.

Design

The review was conducted according to the guide for reporting meta-ethnographic qualitative syntheses eMERGe and the PRISMA guidelines.

Results

The search yielded a total of 2947 studies, out of which 13 were included in the final qualitative synthesis. The interpretive synthesis identified common experiences of people living with mild to moderate dementia, characterised by clusters of themes around worry, emotional experiences, and behavioural reactions in response to the diagnosis of dementia and its symptoms. These represent the components of a conceptual framework of anxiety in mild to moderate dementia, where anxiety is triggered by negative appraisals of living with an irreversible neurodegenerative disease. Stemming from these appraisals of dementia progression and its impact on the person’s overall future, the content of worrisome thoughts and concerns include the loss of self and identity, losing independence and the ability to perform previous activities, concerns about being a burden to loved ones, and worry about the impact on interpersonal relationships.

Conclusion

This conceptualisation of anxiety in dementia, including its subclinical manifestations facilitates the development of psychological interventions and provision of holistic support to people living with dementia.
Influence of automotive headlamp systems on the visibility of targets under different road lighting conditions
Authors: Vogel S , Fiedelak S , Niedling M , Völker S
Published: August 2022

Modern high-resolution headlamp systems are capable of adjusting to different driving situations. However, the existing road lighting is not yet taken into account when setting the headlamp’s light distribution. This article investigates the influence of the automotive headlamp systems on the visibility of targets in different road lighting conditions and proposes a new lighting strategy based on these results. The luminances of square targets of different surface reflectances and at different distances ahead of the vehicle were measured in road lighting designed to meet classes varying from M3 to M6. For each combination the visibility level (VL) of the targets was determined, with road lighting alone and also when additionally illuminating the scene with the car headlamps. The influence of the headlamps on target visibility was found to depend on the road lighting class, the target distance and its reflectance. In some situations, additional light from the headlamp decreased the target VL and therefore the probability that a driver would detect it. Different ranges of headlamp light distribution were proposed for different road lighting classes to bring light only where it is needed.
Measuring Classroom Management in Secondary Settings: Ongoing Validation of the Direct Behavior Rating-Classroom Management
Authors: Sims Wesley A. , Yu Rondy , King Kathleen R. , Zahn Danielle , Mandracchia Nina , Monteiro Elissa , Klaib Melissa
Published: August 2022

Classroom management (CM) practices have a well-established, intuitive, and empirical connection with student academic, social, emotional, and behavioral outcomes. CM, defined as educator practices used to create supportive classroom environments, may be the implementation factor that is most impactful of the universal Tier I supports. Recognizing the importance of CM and existing deficiencies in pre- and in-service training for teachers, schools are increasingly turning to data-driven professional development activities as a solution. The current study continues the validation process of the Direct Behavior Rating-Classroom Management (DBR-CM), an efficient and flexible measure of teacher CM practices in secondary school settings. Data were collected from 140 U.S. Midwest middle and high school classrooms. Results found DBR-CM scores to be significantly correlated with several scores on concurrently completed measures of CM, including those that rely on systematic direct observation and rating scales. Findings continue the accumulation of validity evidence to address extrapolation, generalization, and theory-based inferences underlying the interpretation and intended uses of the DBR-CM. Results are promising and build on previous DBR-CM validation work. Limitations and implications are discussed.
Deconstructing imprisonment: Exploring sentencing discourses in the District Court of New South Wales
Authors: Taylor Sally
Published: August 2022

In Australia, imprisonment remains a popular form of crime control amidst rising costs in prison expenditure and high rates of prison return. While changes to crime rates and to policing policy have impacted the growing prisoner population in recent years, less is known about the language underpinning the courts’ decision to imprison. This article presents the results of a critical discourse analysis on 124 sentencing remarks on imprisonment from the District Court of New South Wales in 2017. Three discourses were identified in the texts as facilitating the justification of a prison sentence: the discourse of control, the discourse of safety and the discourse of duty. These findings highlight the ways in which the prison is constructed and legitimated in the courts, which has implications not only for sentencing policy and practice but also for conceptions and applications of justice more broadly.
Effectiveness and safety of a biosimilar-to-biosimilar switch of the TNF inhibitor etanercept in patients with chronic inflammatory rheumatic diseases
Authors: Kiltz Uta , Tsiami Styliani , Baraliakos Xenofon , Andreica Ioana , Kiefer David , Braun Jürgen
Published: August 2022

Background:

Biosimilar disease-modifying anti-rheumatic drugs (bsDMARDs) has created a financial incentive to encourage switching to cheaper products.

Objectives:

We aim to study the effectiveness and safety of a non-medical bsDMARD-to-bsDMARD switch from originator etanercept (ETN) to bsDMARD ETN (SB4) and successive to another bsDMARD ETN (GP2015) in patients with chronic inflammatory rheumatic diseases in a real-life setting.

Methods:

Retrospective chart review of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA) who had been treated with originator ETN and were switched twice to ETN bsDMARD for non-medical reasons thereafter. All patients received ETN 50 mg/week. Disease activity and physical function was assessed every 12 weeks with standardized questionnaires.

Results:

A total of 100 patients who switched twice [54 RA, 27 axSpA, 19 PsA, mean age 54.3 (15.1), 46% male] were included. Patients with axSpA were younger than RA and PsA patients. Patients with SpA were less likely to receive conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) than RA patients. Duration of treatment with originator ETN before the first switch was 3.3 (2.3) years. Retention rate 6 months after the second ETN bsDMARD switch was 89%. Disease activity and physical function scores remained rather unchanged in patients with RA and axSpA longitudinally, while there was some more fluctuation in PsA patients. Six patients lost efficacy and were switched back to originator ETN in month 6 ( n = 4) or to another mode of action ( n = 2). There were 14 adverse events (AE) reported in eight patients. One patient re-administered bsDMARD GP2015 successfully 3 months after healing of mucosal erosions.

Conclusion:

No relevant change in disease activity and physical function were observed in a non-medical bsDMARD-to-bsDMARD switch scenario. The retention rate after switches from originator ETN to two ETN bsDMARD was close to 90%. Multiple switches resulted in a high adherence rate without clinically important efficacy or safety signals.
Medial patellofemoral ligament reconstruction with simultaneous osteochondral fracture fixation is an effective treatment for adolescent patellar dislocation with osteochondral fractures
Authors: Aitchison Alexandra H , Hidalgo Perea Sofia , Schlichte Lindsay M , Green Daniel W
Published: August 2022

Background:

Osteochondral fractures can occur during patellar dislocation and often require treatment. The purpose of this study is to determine the incidence of recurrent instability and second surgery following osteochondral fracture fixation with concomitant medial patellofemoral ligament reconstruction.

Methods:

A retrospective review of a cohort of 365 medial patellofemoral ligament reconstructions by a single surgeon from 2008 to 2019 was performed to identify patients who underwent simultaneous osteochondral fracture fixation with bioabsorbable nails. Demographic data, surgical details, clinical follow-up, and subsequent procedures were collected.

Results:

Forty medial patellofemoral ligament reconstructions with osteochondral fracture fixation were performed by a single surgeon from 2008 to 2019. The average age at surgery was 14.6 years (range 10.7–19.6 years). The average length of follow-up was 2.6 years (range 0.7–7.0 years). Eleven (28%) patients required a second surgery on the ipsilateral knee. One patient had recurrent instability and required revision medial patellofemoral ligament reconstruction and osteochondral allograft. The other 10 patients underwent a second surgery to address cartilage damage or debridement of nails. Of the four patients who required nail debridement, the average number of nails initially placed was 7 ± 1.7. This was significantly more than the patients who did not require second surgery related to nail debridement (4.1 ± 1.6, p < .05).

Conclusion:

28% of patients required a second procedure, most of which involved debridement of unhealed portions of the osteochondral fracture. At 2.6-year follow-up, only 2% of patients had a failure of their osteochondral fracture fixation requiring a cartilage restoration procedure. Osteochondral fracture fixation in adolescents with patellofemoral instability can be effectively treated with fixation and simultaneous medial patellofemoral ligament reconstruction.

Level of evidence:

level IV,
Contractant behaviour in the pandemic: A real-world survey
Authors: Soper Charles Haward
Published: August 2022

Entirely predictably the Covid pandemic caused material problems in the contracting world, issues such as delivery, payment, and liability, suddenly achieving an undesired prominence. As an empirical researcher, it struck me that I might test my overarching belief that the only valid interest in contract is the performance interest by asking experienced contract professionals how contractants had behaved in the pandemic. During the pandemic, these professionals encountered disputes, a deeper examination of contract provisions, claims, and debates on internal processes. All of which stabilised over time as pragmatic, performance focussed management took the reins. Respondents reacted professionally to events, working to keep contracts alive and reconfigure relationships using a mixture of the formal and the informal, in governance and in the commercial relationship. If contracts did not quite work, respondents engaged, adjusted and trimmed. The same was true for processes – If they did not quite work ‘work arounds’ were created. The paper considers two plausible commercial scenarios in which current contract law might allow an opportunist player to escape from the pandemic bargains made, and argues that contract law should support deal-makers and deter such opportunism.
Food Safety Concerns and Practices Among Palestinian University Students: A Cross-Sectional Study
Authors: Hussien Ahmad A. , Abdellattif Adnan H. , Abumunshar Ali A. , Samara Ahmad , Sharif Labib , Alkaiyat Abdulsalam , Koni Amer A. , Zyoud Sa’ed H.
Published: August 2022

University students constitute a target for risk-reduction interventions regarding food poisoning as they are among those with higher exposure to problematic food. This is particularly important since young adults’ knowledge regarding measures to prevent foodborne illnesses was found to be inadequate. Therefore, the objectives of this study were to assess knowledge, attitudes, and practices regarding food safety and food poisoning among An-Najah National University Students and to investigate the correlation of their knowledge, attitudes, and practices with various socio-demographic characteristics and academic variables. The cross-sectional design was used, and the study occurred at An-Najah National University in Nablus. Data was collected using a native Arabic language face-to-face questionnaire. Verbal consent was obtained before initiation. The questionnaire has four parts that address students’ demographic data, knowledge, attitudes, and practice. A sample of 450 students was invited to complete the questionnaire. Half the respondents were aged 17 to 20, and more than half (57.1%) were females. The median knowledge score was 10.00 [8.75–12.0]. A significant correlation was found between the food poisoning knowledge and attitude scores of students ( r = .339, p < .001), a significant correlation between food poisoning knowledge and attitude scores ( r = .285, p < .001), and a significant correlation between attitude and practice scores ( r = .429, p < .001). The current study found significant correlations between knowledge, attitude, and practices of university students regarding food safety. Female respondents also had better attitudes and more hygienic food practices. The results can help students prepare effective methods to understand food poisoning better and improve their knowledge and awareness. The study also indicates that more comprehensive and focused education regarding food safety is required for this population.
Hospital services under public-private partnerships, outcomes and, challenges: A literature review
Authors: Basabih Masyitoh , Prasojo Eko , Rahayu Amy Yayuk Sri
Published: August 2022

Public-private partnerships (PPP) is used to advance health service access and quality. PPP implementation in hospitals is vital to shorten the service and quality gap. Hospitals are the most significant health budget spender, and this study aimed to identify the PPP effect on hospital performance indicators and its implementation challenges. Thirty-three inclusive articles were filtered and collected from Pubmed, ScienceDirect, Medline, and Sage Publication databases. Results showed that various articles succeeded in implementing PPP and improving the access and quality of health services. Several hospital performance indicators such as diagnosis, therapy, service waiting time, length of stay, referral rate, mortality rate, and patient satisfaction were reported to show better results. However, there was insufficient evidence to say the same on related financial indicators. Policy, resource, communication and trust, risk, and evaluation monitoring were considered challenges in PPP implementation. Its success was not only influenced by major factors such as governance model, finance, politics, and social but also was influenced by the medical practice model applied within the organization. This study contributed to whether PPP affects the hospital performance indicators.
Longitudinal changes in COVID-19 concern and stress: Pandemic fatigue overrides individual differences in caution
Authors: Gassen Jeffrey , Nowak Tomasz J , Henderson Alexandria D , Weaver Sally P , Baker Erich J , Muehlenbein Michael P
Published: August 2022

Background:

Pandemic fatigue describes a phenomenon whereby individuals experience a decrease in COVID-19 concern over time, despite their risk for infection remaining stable, or even increasing. Individual differences in the experience of pandemic fatigue may have important implications for people’s adherence to public health recommendations.

Design and methods:

Using data collected from a large community cohort in McLennan County, TX, longitudinal changes in COVID-19-related concern, stress, and affect across three appointments separated by approximately 4 weeks (July–November 2020) were examined. About 495, 349, and 286 participants completed one, two, and three appointments, respectively. Changes to stress physiology and local travel over time were also analyzed.

Results:

Results of a latent class growth analysis revealed four distinct classes of individuals: (a) low concern, low stress, (b) moderate concern, moderate stress, (c) moderate concern, low stress, and (d) high concern, high stress. Despite differences between latent classes in initial levels of concern, stress, and negative affect, levels of each variable decreased over time for all groups. While this reduction of concern did not coincide with changes in local travel, it was reflected in heart rate and blood pressure.

Conclusions:

Together, these results suggest a general trend of pandemic fatigue in the sample, even for those with moderate-to-high levels of initial COVID-19 stress and concern. Such findings may provide insights into the expected challenges of promoting compliance with public health recommendations as the pandemic continues.
Cemiplimab for Locally Advanced Cutaneous Squamous Cell Carcinoma: A Case Series of 3 Unique Scenarios
Authors: Akhtar Komal , Sravanthi Metlapalli Venkata , D’Angelo Josephine , Sivapiragasam Abirami
Published: August 2022

Cemiplimab, a monoclonal antibody directed against programmed death receptor 1 (PD-1), has shown promising results in cutaneous squamous cell carcinoma (cSCC). In a nonrandomized trial where cemiplimab 3 mg/kg was given every 2 weeks for up to 96 weeks, a 44% response rate was noted. This case series discusses 3 unique scenarios of patients with advanced cSCC treated with cemiplimab. The first case is of an end stage kidney disease (ESKD) patient with failed living donor kidney transplant who had developed recurrent cSCC despite several excisions and topical 5-flurouracil and acitretin therapy. He received 8 cycles of cemiplimab leading to resolution. This case serves as an example of the safety and efficacy of cemiplimab in a complex patient who is a kidney transplant recipient on hemodialysis. The second case describes an elderly gentleman with inoperable cSCC initially treated with radiotherapy who later received 9 cycles of cemiplimab for recurrent metastatic disease with excellent response. This case supports the safe and effective use of cemiplimab in an elderly patient. In the third case, cSCC presented itself as a large fungating mass that would have otherwise necessitated limb amputation and was successfully treated with 18 cycles of cemiplimab. This case highlights the dramatic response to cemiplimab obviating the need for surgical intervention and resulting in limb salvage.
Shaping Better Rehabilitation to Chronic Obstructive Pulmonary Disease Patients: Experiences of Nurses and Colleagues With an Interdisciplinary Telerehabilitation Intervention
Authors: Simonÿ Charlotte , Neerup Andersen Marianne , Hansen Rasmus Gormsen , Schrøder Lisbeth , Jensen Therese Gjerde , Bodtger Uffe , Birkelund Regner , Beck Malene
Published: August 2022

In order to evaluate the reach of a collaborative cross-sectoral telerehabilitation intervention to patients with Chronic Obstructive Pulmonary Disease (COPD), this study investigates how nurses and interdisciplinary colleagues experienced working with it. In two focus group interviews, the experiences of working in the empowerment and tele-based >C☺PD-Life>> program were examined among three nurses and four interdisciplinary colleagues. Data were analyzed with inspiration from Ricoeur’s theory of narrative and interpretation and discussed with Gittell’s theory of relational coordination. Nurses and colleagues experienced that the intervention paved the way for unique patient-professional coordination and interdisciplinary cross-sectoral teamwork that allowed double-layered relational coordination, focusing holistically on patients’ lived challenges in everyday life with COPD. By this rehabilitation setup, nurses and colleagues are perceived as educated to deliver high standard personalized support, raising professional pride and confidence. The findings can inspire future health-promoting initiatives within nursing support related to patients afflicted with COPD.
A spatial autoregressive geographically weighted quantile regression to explore housing rent determinants in Amsterdam and Warsaw
Authors: Tomal Mateusz , Helbich Marco
Published: August 2022

A hedonic approach is typically performed to identify housing rental or sales price determinants. However, standard hedonic regression models disregard spatial autocorrelation of prices and heterogeneity of housing preferences across space and over price segments. We developed a spatial autoregressive geographically weighted quantile regression (GWQR-SAR) to address these shortcomings. Using data on the determinants of residential rental prices in Warsaw (Poland) and Amsterdam (The Netherlands) as case studies, we applied GWQR-SAR and rigorously compared its performance with alternative mean and quantile hedonic regressions. The results revealed that GWQR-SAR outperforms other models in terms of fitting accuracy. Compared with mean regressions, GWQR-SAR performs better, especially at the tails of the dependent variable distribution, where non-quantile models overestimate low rent values and underestimate high ones. Policy recommendations for the development of private residential rental markets are provided based on our results, which incorporate spatial effects and price segment requirements.
Voices and Perspectives of Dalit Elected Women Representatives in Local Governance and Politics in Kerala, India
Authors: Akhila P.
Published: August 2022

This article explores how gender socialization as women along with other intersecting identities influence the perspectives of Dalit Elected Women Representatives (EWRs) on power relations in the political space of Kerala. The purpose of the article is to understand the perspectives of Dalit EWRs on power relations in local governance, which reveal the barriers, their interest and aspirations in local governance and politics. The perspectives are elicited through detailed interviews of EWRs for two time periods. The study finds that EWRs participation in local electoral politics and the extent to gain space for decision-making would depend on their ability to overcome barriers to their representation and acceptance in decision-making fora. They also faced caste discrimination and allegations of favouritism in the governance.
S100A8/A9 drives the formation of procoagulant platelets through GPIbα
Authors: Colicchia Martina , Schrottmaier Waltraud C. , Perrella Gina , Reyat Jasmeet S. , Begum Jenefa , Slater Alexandre , Price Joshua , Clark Joanne C. , Zhi Zhaogong , Simpson Megan J. , Bourne Joshua H. , Poulter Natalie S. , Khan Abdullah O. , Nicolson Phillip L. R. , Pugh Matthew , Harrison Paul , Iqbal Asif J. , Rainger George E. , Watson Steve P. , Thomas Mark R. , Mutch Nicola J. , Assinger Alice , Rayes Julie
Published: August 2022

S100A8/A9, also known as “calprotectin” or “MRP8/14,” is an alarmin primarily secreted by activated myeloid cells with antimicrobial, proinflammatory, and prothrombotic properties. Increased plasma levels of S100A8/A9 in thrombo-inflammatory diseases are associated with thrombotic complications. We assessed the presence of S100A8/A9 in the plasma and lung autopsies from patients with COVID-19 and investigated the molecular mechanism by which S100A8/A9 affects platelet function and thrombosis. S100A8/A9 plasma levels were increased in patients with COVID-19 and sustained high levels during hospitalization correlated with poor outcomes. Heterodimeric S100A8/A9 was mainly detected in neutrophils and deposited on the vessel wall in COVID-19 lung autopsies. Immobilization of S100A8/A9 with collagen accelerated the formation of a fibrin-rich network after perfusion of recalcified blood at venous shear. In vitro, platelets adhered and partially spread on S100A8/A9, leading to the formation of distinct populations of either P-selectin or phosphatidylserine (PS)-positive platelets. By using washed platelets, soluble S100A8/A9 induced PS exposure but failed to induce platelet aggregation, despite GPIIb/IIIa activation and alpha-granule secretion. We identified GPIbα as the receptor for S100A8/A9 on platelets inducing the formation of procoagulant platelets with a supporting role for CD36. The effect of S100A8/A9 on platelets was abolished by recombinant GPIbα ectodomain, platelets from a patient with Bernard-Soulier syndrome with GPIb-IX-V deficiency, and platelets from mice deficient in the extracellular domain of GPIbα. We identified the S100A8/A9-GPIbα axis as a novel targetable prothrombotic pathway inducing procoagulant platelets and fibrin formation, in particular in diseases associated with high levels of S100A8/A9, such as COVID-19.
Deferiprone for transfusional iron overload in sickle cell disease and other anemias: open-label study of up to 3 years
Authors: Elalfy Mohsen S. , Hamdy Mona , El-Beshlawy Amal , Ebeid Fatma S. E. , Badr Mohamed , Kanter Julie , Inusa Baba , Adly Amira A. M. , Williams Suzan , Kilinc Yurdanur , Lee David , Fradette Caroline , Rozova Anna , Temin Noemi Toiber , Tricta Fernando , Kwiatkowski Janet L.
Published: August 2022

Long-term safety and efficacy data on the iron chelator deferiprone in sickle cell disease (SCD) and other anemias are limited. FIRST-EXT was a 2-year extension study of FIRST (Ferriprox in Patients With Iron Overload in Sickle Cell Disease Trial), a 1-year, randomized noninferiority study of deferiprone vs deferoxamine in these populations. Patients who entered FIRST-EXT continued to receive, or were switched to, deferiprone. Altogether, 134 patients were enrolled in FIRST-EXT (mean age: 16.2 years), with mean (SD) exposure to deferiprone of 2.1 (0.8) years over the 2 studies. The primary end point was safety. Secondary end points were change in liver iron concentration (LIC), cardiac T2∗, serum ferritin (SF), and the proportion of responders (≥20% improvement in efficacy measure). The most common adverse events considered at least possibly related to deferiprone were neutropenia (9.0%) and abdominal pain (7.5%). LIC (mg/g dry weight) decreased over time, with mean (SD) changes from baseline at each time point (year 1, −2.64 [4.64]; year 2, −3.91 [6.38]; year 3, −6.64 [7.72], all P < .0001). Mean SF levels (μg/L) decreased significantly after year 2 (−771, P = .0008) and year 3 (−1016, P = .0420). Responder rates for LIC and SF increased each year (LIC: year 1, 46.5%; year 2, 57.1%; year 3, 66.1%; SF: year 1, 35.2%; year 2, 55.2%; year 3, 70.9%). Cardiac T2∗ remained normal in all patients. In conclusion, long-term therapy with deferiprone was not associated with new safety concerns and led to continued and progressive reduction in iron load in individuals with SCD or other anemias. The trial was registered at www.clinicaltrials.gov as #NCT02443545.
Utility of whole genome sequencing in assessing risk and clinically relevant outcomes for pulmonary fibrosis
Authors: Zhang David , Newton Chad A. , Wang Binhan , Povysil Gundula , Noth Imre , Martinez Fernando J. , Raghu Ganesh , Goldstein David , Garcia Christine Kim
Published: August 2022

Background

Whole genome sequencing (WGS) can detect variants and estimate telomere length. The clinical utility of WGS in estimating risk, progression and survival of pulmonary fibrosis patients is unknown.

Methods

In this observational cohort study, we performed WGS on 949 patients with idiopathic pulmonary fibrosis or familial pulmonary fibrosis to determine rare and common variant genotypes, estimate telomere length and assess the association of genomic factors with clinical outcomes.

Results

WGS estimates of telomere length correlated with quantitative PCR (R=0.65) and Southern blot (R=0.71) measurements. Rare deleterious qualifying variants were found in 14% of the total cohort, with a five-fold increase in those with a family history of diseaseversusthose without (25%versus5%). Most rare qualifying variants (85%) were found in telomere-related genes and were associated with shorter telomere lengths. Rare qualifying variants had a greater effect on telomere length than a polygenic risk score calculated using 20 common variants previously associated with telomere length. The common variant polygenic risk score predicted telomere length only in sporadic disease. Reduced transplant-free survival was associated with rare qualifying variants, shorter quantitative PCR-measured telomere lengths and absence of theMUC5Bpromoter (rs35705950) single nucleotide polymorphism, but not with WGS-estimated telomere length or the common variant polygenic risk score. Disease progression was associated with both measures of telomere length (quantitative PCR measured and WGS estimated), rare qualifying variants and the common variant polygenic risk score.

Conclusion

As a single test, WGS can inform pulmonary fibrosis genetic-mediated risk, evaluate the functional effect of telomere-related variants by estimating telomere length, and prognosticate clinically relevant disease outcomes.
Destructive inflammatory reaction after an autologous retinal pigment epithelium and choroid transplantation: no detection of an auto-immune response
Authors: van Romunde Saskia H. M. , Vergouwen Daphne P. C. , Iacovello Daniela , Roelen Dave L. , Verdijk Robert M. , ten Berge Josianne C. E. M. , Pertile Grazia , Schreurs Marco W. J. , van Meurs Jan C.
Published: August 2022

Purpose

Five patients who underwent uncomplicated retinal pigment epithelium (RPE)-choroid transplantation for neovascular age-related macular degeneration developed a destructive inflammatory reaction causing subretinal fluid accumulation and extensive RPE atrophy in the graft. We hypothesized that this inflammation could be caused by an auto-immune response against the graft, resulting in circulating auto-antibodies. The aim of our study was to examine a potential autoimmune origin, which would allow a more targeted therapy approach.

Methods

Five above-mentioned patients and four control groups of five patients each were included: 1) after uncomplicated RPE-choroid transplantation, 2) after full macular translocation, 3) treated with anti-vascular endothelial growth factor, and 4) healthy controls. Histopathology of rejected graft tissue was performed using standard procedures. Presence of RPE-choroid autoantibodies in serum was examined by indirect immunofluorescence and Western blot, and human leukocyte antigen (HLA) typing was performed.

Results

Histopathological examination of an explanted graft showed infiltration of T-lymphocytes and macrophages in the choroid and RPE, and an increased number of B-cell lymphocytes were found in the choroid. Indirect immunofluorescence showed weak RPE-choroid autoantibody immunoreactivity in three patients of different groups. Western blot did not show specific RPE-choroid autoantibody immunoreactivity and no difference of HLA genotypes between the groups was found.

Conclusions

Although local mononuclear inflammatory cell infiltration and a high number of B-lymphocytes were observed in an explanted graft, we did not detect serological evidence of an autoimmune origin of the postoperative inflammation using direct immunofluorescence and Western Blot. Alternatively, the graft failure may have been caused by local innate inflammation, triggered by breakdown of tolerance. Based on our current findings of this small study group, we have no rationale to pursue therapies targeted towards autoreactive graft failure. More research is needed to confirm our findings.
Semen parameters are seriously affected in acephalic spermatozoa syndrome
Authors: Ying Li-juan , Yu Lin , Yang Tingting , Wu Ying-bi , Xu Jin-yan , Jia Ye-lin , Zheng Yan , Li Fuping
Published: August 2022

Background

Previous studies have reported that some patients with headless spermatozoa have poor semen quality, but there has been no published systematic analysis of semen quality in patients with different proportions of headless spermatozoa in semen. We aimed to explore the association of acephalic spermatozoa syndrome and semen quality in men with distinct proportions of headless spermatozoa.

Material and methods

Semen parameter values in patients for whom headless spermatozoa were found in the ejaculates was studied and compared to that of 413 age-matched prenatal examination patients. All semen samples were analyzed following the same methodology in a single laboratory.

Results

All semen parameter values except semen volume were negatively (P < 0.05) correlated with the proportion of headless spermatozoa. The semen samples were divided into four groups on the basis of the proportion of headless spermatozoa (PHS) as follows: 0 < PHS ≤ 5% (n = 172, Group A1); 5 < PHS ≤ 10% (n = 76, Group A2); 10 < PHS ≤ 20% (n = 71, Group B); and PHS > 20% (n = 71, Group C). In Group A1, only one semen parameter value (progressive motility) was lower than those of the control group, but in Group A2, this increased to five (sperm vitality, normal sperm morphology, sperm motility, VCL (curvilinear velocity) and ALH (amplitude of lateral head displacement)). Worse still, all semen parameter values were significantly lower in Group B and Group C than in the control group (P < 0.05).

Conclusions

Semen samples containing headless spermatozoa tend to have lower quality than samples without headless spermatozoa. Increases in the proportion of headless spermatozoa in semen are associated with decreased semen quality. We suggest that headless spermatozoa should be seriously assessed and accurately counted in semen analysis, especially for ejaculate in which the proportion of headless spermatozoa exceeds 5%.