bluuebunny/crossref_metadata_2025 huggingface dataset:
“Over My Dead Body”: Wives’ Influence in Family Business Succession
Authors: Cosson Barbara , Gilding Michael
Published: October 2021

The family business literature barely addresses wives’ influence in family business succession. Where it does so, the result is often tokenistic, stereotypical, and imprecise. Drawing on 34 in-depth interviews, this article makes three contributions. First, it identifies wives’ critical influence in family business succession through socialization across the life span of the family business; specifically, through normative, interactive, and experiential socialization. Second, it demonstrates the diverse dynamics and impact of wives’ influence on family business continuity. Third, it highlights the particular significance of experiential socialization, whereby changing expectations of marriage and family life have amplified wives’ influence in succession outcomes.
A Just Weight and Measure: Embodied Economics and the Relationship between Worship and Economic Transaction
Authors: Abrego Joshua
Published: October 2021

The concept of a ‘just weight and measure’ within the Bible is one that has insightful value for Christian ethics and economic transactions. Considering that in many situations law and judicial systems within Western society are not capable of completely constraining unethical economic transactions, what society requires are alternative motivations to enact ethical economic transactions. This article is focused on proposing a possible motivation for Christians considering the ever-growing complexities within the marketplace. It draws on insights on the concept of a ‘just weight and measure’ in Deuteronomy and its conceptual use within the books of the eighth-century prophets. A primary insight that is highlighted is the relationship between the unethical economic transactions in eighth-century Israel and God's rejection of their cultic services. When applied analogically to contemporary contexts, lessons can be gleaned from the concept of a ‘just weight and measure’ for Christian ethical economic transactions.
An investigation of emerging COVID-19 research trends and future implications for LIS field: A bibliometric mapping and visualization
Authors: Sheikh Arslan , Siddique Nadeem , Qutab Saima , Khan Muhammad Ajmal , Mahmood Khalid
Published: October 2021

The COVID-19 epidemic has proved a nightmare for human beings living all across the globe. It has severely affected all segments of human life. Consequently, enormous research has been conducted to assess and counter this global pandemic. This study reports finding of a bibliometric analysis on COVID-19 related literature published in the Library and Information Science journals, to identify current research trends and to suggest future directions for further research. It reveals a substantial increase in LIS publications on COVID-19 in the year 2020. The findings of the study are presented in two sections: first, the research productivity analysis provides an overview of the prominent authors, sources, institutions, and countries that published about COVID-19 in the LIS field. The second section offers a co-word thematic analysis of the significant emerging themes that provide an insight into current challenges faced by libraries and suggest future trends for research and practice in post-COVID era. The study exposes 5 major research themes and 11 sub-themes.
Combination of silk fabric and natural rubber for the development of green composites: Influence of curing on mechanical and thermal properties
Authors: Kumar M Thanuj , Shetty S G Sanga , Kalkornsurapranee Ekwipoo , Songtipya Ladawan , Nakaramontri Yeampon , Johns Jobish
Published: October 2021

Unmodified natural rubber is not suitable for any elstomeric applications. Therefore, it is appropriate to modify natural rubber chemically to enhance the stability, which can be termed as vulcanization. Incorporation of fibers/fabrics is a common method to increase the stability of natural rubber along with chemical modification. Natural rubber-based composites have been prepared by the addition of silk fabric into natural rubber. The matrix material for the composite is glutaraldehyde cured natural rubber. Silk is an ecofriendly and biodegradable material with excellent tensile strength. When such kind of fabric is introduced into the vulcanized rubber as the matrix, all the physical properties were found to be enhanced considerably. Tensile properties in terms of ultimate tensile strength, elongation at break, and modulus of elasticity are measured for the composites of natural rubber/silk fabric at various glutaraldehyde concentrations. Thermogravimetric analysis and temperature scanning stress relaxation techniques are employed to evaluate the thermal stability of the resulting composites. Effects of glutaraldehyde addition on the physical properties of the composite were studied in detail. Considerable enhancement in the stability of natural rubber in terms of tensile properties, thermal stability, and solvent resistance is noticed up on the incorporation of silk fabric as well as glutaraldehyde curing.
Seeking alternatives, asserting choices: Dr Mahendralal Sarkar's life in medicine and science
Authors: Singh Dhrub Kumar
Published: October 2021

This article examines the medical life of a native physician who embraced homoeopathy despite being trained in the dominant pathy i.e. allopathy at the prestigious Calcutta Medical College in the 1860s. Mahendralal Sarkar, the physician in focus, was one of the first famous converts to homoeopathy. His seeking of an alternative option created space and legitimacy for homoeopathy. Through the journal Calcutta Journal of Medicine that Sarkar founded, he, with great ability, asserted and defended his right as a physician to decide in favour of homoeopathy. Sarkar gradually established himself as an accomplished homoeopath and was recognised as an important public figure of Calcutta. The odds and opposition he faced convinced him to embark on a great task of the cultivation of science as, in his view, the inculcation of the spirit of science was the need of the day to break the orthodoxy and mitigate prejudices of the medical profession and society at large.
Service Workers’ Well-Being During COVID-19: A Strengths-Based Inclusive Theory of Work Perspective
Authors: Owens Rhea L. , Meierding Erika E. , Allan Blake A.
Published: October 2021

This study tested the Strengths-Based Inclusive Theory of Work (S-BIT of Work), a vocational theory that emphasizes positive psychological and cultural factors, among a sample of service industry workers during COVID-19. Service industry workers ( N = 320) were recruited via social media sources across the United States, and structural equation modeling was used to examine the model. This model included privilege and COVID-19 impact as contextual variables; organizational support and workplace dignity as promotive workplace variables; hope, strengths use, adaptability, empowerment, and perceived COVID-19 threat as individual variables; and fulfilling work and psychological distress as outcome variables. Privilege and workplace dignity were identified as particularly important variables; results suggested privilege was positively associated with a promotive work context and negatively related to psychological distress. Additionally, the greater the amount of privilege and dignity the service industry workers experienced, the greater their positive individual characteristics were able to flourish.
Technology-enhanced weight-loss program in multiple-cat households: a randomized controlled trial
Authors: Hadar Barr N , Lambrecht Kenneth J , Poljak Zvonimir , Coe Jason B , Stone Elizabeth A , Verbrugghe Adronie , Bernardo Theresa M
Published: October 2021

Objectives

The objectives of this study were to determine whether a technology-enhanced weight-loss program, using a home pet health technology ecosystem, is an effective tool in feline weight-loss management in multiple-cat households and to evaluate its impact on cat behavior.

Methods

The study was a prospective parallel unmasked block-randomized controlled trial comparing two weight loss intervention groups: (1) traditional group with dietary restriction alone (n = 9); (2) technology group that used dietary restriction, digital scales, smart feeders, activity monitors and pet treat cameras (n = 6). A 12-week weight-loss program of client-owned indoor-only two- or three-cat households with at least one overweight cat was conducted in Canada and the USA. Owner impressions of the technology, weight loss rates, smart feeder data, activity monitor data and health-related quality of life (HRQoL) were assessed.

Results

The study was completed by 9/15 traditional group and 6/10 technology group cats. Dropouts were mainly due to owner issues unrelated to the study. The pet health technology ecosystem received favorable reviews (six responders). Smart feeders and home scales were perceived as valuable additions, while activity monitors and pet treat cameras were valued lower. The average weekly weight-loss rate (percent loss of initial body weight) was higher ( P = 0.036) in the technology group (0.694%) than in the traditional group (0.175%). Although not associated with weight-loss rates, technology group cats trended toward grazing feeding patterns and decreased daily activity counts, while HRQoL increased, on average, for all cats.

Conclusions and relevance

This introductory investigation suggests that a technology-enhanced weight-loss program would be accepted by cat owners and may deliver advantageous outcomes in multiple-cat households, providing an effective and practical tool in feline weight-loss strategies that will continue to evolve as new technologies become available. It also illustrates the potential value of data gathered from home monitoring devices and digital diaries, providing deeper insights into pet behavior.
Numerical analysis and optimization of rectangular texture for gas foil thrust bearing
Authors: He Zhenpeng , Zhang Chun , Li Jianqiang , Zhao Yuanyuan , Sun Aijun
Published: October 2021

Accurate surface texture design is of great significance to improve the performances of gas bearings. In this article, the finite difference method and Newton’s method were combined to obtain the oil film pressure distribution, and the effect of rectangular groove on the lubrication performance was analyzed by changing representative texture parameters. The results show that the performances were more affected by the rectangular texture size compared with the distribution and the bottom shape of texture. The increasing of the surface texture number can only enhance the stability of the bearing. The bearing can provide 30% more bearing capacity by choosing larger size, radial arrangement and plane bottom. These results and analysis can provide technical reference for the bearing texture design.
Thermo-physical and tribological characteristics of ionic liquid-based rice bran oil as green cutting fluid
Authors: Singh Aswani K , Sharma Varun
Published: October 2021

During machining, the cutting fluids play an essential role in cooling and lubrication. In order to reduce the friction forces, the excessive amount of the cutting fluids are generally used. This, in turn, leads to wastage of the cutting fluids which results in a serious impact on the environment, health and cost of production. Therefore, the judicious use of lubricants is the foremost concern in the manufacturing industry. In order to mitigate these drawbacks, various alternatives have been developed in the last decade. In the present paper, ionic liquids have been proved as favourable sustainable alternative additives in the base oil. The effect of alkyl chain length of ionic liquids with base oil on the thermo-physical and tribological characteristics of cutting fluids including viscosity, wettability, anticorrosion behaviour, thermal stability, and coefficient of friction have been analysed. In the present study, pyrrolidinium and hexafluoro-phosphate (PF6) have been used as cation and anion, respectively, with rice bran oil as base oil. The five different ionic liquids have been dispersed in base oil by 1.0 wt%. It has been found that longer alkyl chain length showed the favourable results as compared to the shorter one. Results indicated that ionic liquid based cutting fluid attained ample enhanced thermophysical and tribological properties as compared to the neat rice bran oil. There has been 5.08% and 4.29% improvement in viscosity and thermal conductivity for IL4 + RBO in comparison to neat RBO. In addition, the wettability, coefficient of friction, and wear volume have been reduced by 20.34%, 53.79% and 57.87% correspondingly.
SwirlProp: A tool for sound propagation and attenuation in swirling flows
Authors: Maldonado Ana Luisa P , Astley R Jeremy
Published: October 2021

The current trends for next generation turbofan engines are towards shorter nacelles and increased distances between the fan and the outlet guide vanes. This leads to an overall reduction in lined surface areas as well as an increase in the relative importance of the interstage liner, which is the liner placed between the rotor blades and the stator vanes. So far most of the efforts have been on liners for intakes and bypass ducts. The interstage is different in that the liner is subject to a mean flow with a strong swirl component and shear. The SwirlProp code was developed to contribute to understanding and predicting the effect of the swirl on liner attenuation. The code is based on the linearized Euler equations together with the Ingard–Myers boundary condition. An eigenvalue problem is formulated and discretized using a finite difference method. The code is exhaustively compared against predicted values obtained by other methods for uniform, sheared and swirling mean flows and hard-walled and lined ducts. A cross-validation between SwirlProp and an in-house code from Rolls-Royce was carried out for a more realistic case. Also, details on the implementation of the boundary condition are proposed and details are presented.
Contrast-Associated Acute Kidney Injury in Patients with and without Diabetes Mellitus Undergoing Computed Tomography Angiography and Local Thrombolysis for Acute Lower Limb Ischemia
Authors: Butt Talha , Lehti Leena , Apelqvist Jan , Gottsäter Anders , Acosta Stefan
Published: October 2021

Purpose

Repetitive iodinated contrast media exposure may be harmful for the kidneys. The aim of the present study was to evaluate if patients with diabetes mellitus (DM) undergoing CT angiography (CTA) and local continuous thrombolysis for acute lower limb ischemia (ALI) had an increased risk of developing contrast-associated acute kidney injury (CA-AKI) compared to patients without DM. Methods: This is a retrospective study of patients undergoing CTA and local continuous thrombolysis due to ALI between 2001 and 2018. CA-AKI was defined as a 25% increase in serum creatinine within 72 hours after latest contrast administration. Results: There was no difference ( P = .30) in the frequency of CA-AKI between patients with (27.9%; n = 43) and without DM (20.6%; n = 170). Among patients with CA-AKI, patients with DM had a lower ( P < .001) estimated glomerular filtration rate (eGFR) at discharge (55 ml/min/1.73 m2) than at admission (70 ml/min/1.73 m2), while no such difference was found in the group without DM ( P = .20). The gram-iodine dose/eGFR ratio was higher ( P < .001) in patients with CA-AKI (median 1.49, [IQR 1.34-1.81]) than in those who did not develop CA-AKI (median 1.05 [IQR 1.00-1.13]). There was a trend that gram-iodine dose/eGFR ratio (OR 1.42/standard deviation increment, 95% CI 1.00-2.02; P = .050) was associated with an increased risk of CA-AKI, after adjusting for DM, age, and gender. Conclusions: The frequency of CA-AKI was high after CTA and local continuous thrombolysis for ALI without shown increased frequency for the DM group. Among patients with CA-AKI, however, patients with DM had worse renal function at discharge than those without DM. The gram-iodine dose/eGFR ratio in these patients needs to be lower to improve renal outcomes, particularly in patients with DM.
Ligustrazine activate the PPAR-γ pathway and play a protective role in vascular calcification
Authors: Li Hui , Yang Min
Published: October 2021

Objective

The purpose of this study was to explore the role of ligustrazine in vascular calcification.

Methods

After β-GP stimulation, vascular smooth muscle cells (VSMCs) were detected by Alizarin Red Staing staining. Calcium content and alkaline phosphatase (ALP) activity were detected by intracellular calcium assay kit and ALP assay kit, respectively. The expression of peroxisome proliferation-activated receptor (PPAR-γ) pathway–related proteins was detected by Western blot. PPAR-γ, MSX2, osteopontin (OPN), sclerostin, and BGP were detected by RT-PCR.

Results

β-GP induced the decreased activity and expression of PPAR-γ and ALP in VSMCs, while ligustrazine activated the expression of PPAR-γ. Through activation of PPAR-γ, ligustrazine decreased β-GP–induced VSMC calcification, decreased the expression of markers of osteogenesis and chondrogenic differentiation, and increased the expression of VSMC markers.

Conclusion

Ligustrazine activates the PPAR-γ pathway and plays a protective role in vascular calcification.
What Are Patient Preferences for Integrated Behavioral Health in Primary Care?
Authors: Dunn Julia Alexandra , Chokron Garneau Hélène , Filipowicz Heather , Mahoney Megan , Seay-Morrison Timothy , Dent Kaitlin , McGovern Mark
Published: October 2021

Background: Behavioral health services, integrated into primary care practices, have become increasingly implemented. Although patient satisfaction has been studied, limited information exists about patient preferences for integrated behavioral health in primary care and how perceptions may vary. Objective: To determine patient preferences for integrated behavioral health within primary care and explore differences across patient groups. Methods: A self-report survey was distributed within a quality improvement initiative in an academic health system. A brief 8-item self-report questionnaire of perceptions and preferences for integrated behavioral health was administered to 752 primary care patients presenting before their visits at two primary care clinics. Participation was voluntary, responses were anonymous, and all patients presenting during a three-week timeframe were eligible. Results: In general, patients preferred to have behavioral health concerns addressed within primary care (n = 301; 41%) rather than referral to a specialist (7.5%; n = 55). There was no evidence of variation in preferences by demographic characteristics. Comfort levels to receive behavioral health services ( P < .001) and perceived needs being met were significantly associated with preferences for receiving IBHPC ( P < .001). Conclusion: This project provided valuable data to support the implementation of integrated behavioral health services in primary care clinics. In general, patients prefer to have behavioral health issues addressed within their primary care experience rather than being referred to specialty mental health care. This study adds to an expanding pool of studies exploring patient preferences for integrated behavioral health in primary care.
Increase in Achilles Tendon Rupture Surgery in Japan: Results From a Nationwide Health Care Database
Authors: Yamaguchi Satoshi , Kimura Seiji , Akagi Ryuichiro , Yoshimura Kensuke , Kawasaki Yohei , Shiko Yuki , Sasho Takahisa , Ohtori Seiji
Published: October 2021

Background:

Nationwide epidemiologic studies in Scandinavian countries have shown that the incidence of Achilles tendon ruptures (ATRs) has increased, and the rate of surgical treatment has declined markedly in the past decade. However, there is a lack of national-level data on the trend of ATRs and surgical procedures in other regions.

Purpose:

To clarify the trend in the incidence of ATRs and the proportion of surgery using the nationwide health care database in Japan.

Study Design:

Descriptive epidemiology study.

Methods:

Age- and sex-stratified data on the annual number of ATRs and surgical procedures between 2010 and 2017 were obtained from the Japanese national health care database, which includes almost all inpatient and outpatient medical claims nationwide. The Japanese population data were also obtained from the population census. The change in the annual incidence of ATRs per 100,000 people was assessed using a Poisson regression analysis. The trend in the annual proportion of surgeries relative to the occurrence of tendon ruptures was determined using a linear regression analysis.

Results:

A total of 112,601 ATRs, with men accounting for 67%, were identified over 8 years. Patients aged ≥60 years accounted for 27,106 (24%), while those aged 20 to 39 years and 40 to 59 years accounted for 36,164 (32%) and 49,331 (44%), respectively. The annual incidence of ATR ranged from 12.8/100,000 to 13.9/100,000 (women, 8.2-8.9/100,000; men, 17.2-19.5/100,000), which did not change over the study period ( P = .82). Moreover, the annual incidences did not change across sexes and age categories. The annual proportion of surgery increased significantly, from 67% in 2010 to 72% in 2017 ( P = .003). The annual proportions increased across sexes and age categories except for women aged 40 to 59 years.

Conclusion:

The incidence of ATR did not change between 2010 and 2017, according to the Japanese nationwide health care database. Furthermore, the proportion of surgical treatment increased during the study period. Overall, 70% of patients underwent surgical treatment. This study suggested that the trend in ATR and surgery differed across regions.
Leadership in Crisis: Lessons from India
Authors: Mahapatra Gopal P. , Kalra Tanvika
Published: October 2021

Society is going through transformation and disruption from time immemorial. Globalisation, liberalisation of the economies and technological disruptions have created unprecedented eventualities in the political, economic, social and industrial domains. The recent COVID-19 pandemic has added enhanced complexities to these domains. The role of leaders, thus, becomes an integral part of addressing these complexities. The authors argue that the leadership role in the business world appears to have transformed from top-down autocratic leadership to inclusive leadership; with each of the stakeholders having critical roles to play.

The article summarises the lessons learnt from the Indian texts, scriptures and philosophy that contemporary leaders can consider and possibly adopt. A few examples from the scriptures and texts are discussed, linking to current leadership practices. Further, leaders are encouraged to expand their roles to address well-being, compassion, empathy and trust. To be more effective and impactful, the leaders need to continuously reinvent themselves with changing times and contexts.
Allogeneic transplant and CAR-T therapy after autologous transplant failure in DLBCL: a noncomparative cohort analysis
Authors: Hamadani Mehdi , Gopal Ajay K. , Pasquini Marcelo , Kim Soyoung , Qiu Xianmiao , Ahmed Sairah , Lazaryan Aleksandr , Bhatt Vijaya Raj , Daly Andrew , Lulla Premal , Ciurea Stefan , Gauthier Jordan , Agrawal Vaibhav , Grover Natalie S. , Lekakis Lazaros , Modi Dipenkumar , Dahi Parastoo B. , Herr Megan M. , Johnson P. Connor , Hashmi Hamza , Hematti Peiman , Locke Frederick L.
Published: October 2021

Allogeneic transplant (alloHCT) and chimeric antigen receptor modified (CAR)-T cell therapy are potentially cuarative options of diffuse large B-cell lymphoma (DLBCL) relapsing after an autologous (auto)HCT. Although the Center for International Blood and Marrow Transplant Research (CIBMTR) prognostic model can predict outcomes of alloHCT in DLBCL after autoHCT failure, corresponding models of CAR-T treatment in similar patient populations are not available. In this noncomparative registry analysis, we report outcomes of patients with DLBCL (≥18 years) undergoing a reduced intensity alloHCT or CAR-T therapy with axicabtagene ciloleucel during 2012 to 2019 after a prior auto-HCT failure and apply the CIBMTR prognostic model to CAR-T recipients. A total of 584 patients were included. The 1-year relapse, nonrelapse mortality, overall survival (OS), and progression-free survival for CAR-T treatment after autoHCT failure were 39.5%, 4.8%, 73.4%, and 55.7%, respectively. The corresponding rates in the alloHCT cohort were 26.2%, 20.0%, 65.6%, and 53.8%, respectively. The 1-year OS of alloHCT recipients classified as low-, intermediate- and high/very high-risk groups according to the CIBMTR prognostic score was 73.3%, 59.9%, and 46.3%, respectively (P = .002). The corresponding rates for low-, intermediate-, and high/very high-risk CAR-T patients were 88.4%, 76.4%, and 52.8%, respectively (P < .001). This registry analysis shows that both CAR-T and alloHCT can provide durable remissions in a subset of patients with DLBCL relapsing after a prior autoHCT. The simple CIBMTR prognostic score can be used to identify patients at high risk of treatment failure after either procedure. Evaluation of novel relapse mitigations strategies after cellular immunotherapies are warranted in these high-risk patients.
ASH Research Collaborative: a real-world data infrastructure to support real-world evidence development and learning healthcare systems in hematology
Authors: Wood William A. , Marks Peter , Plovnick Robert M. , Hewitt Kathleen , Neuberg Donna S. , Walters Sam , Dolan Brendan K. , Tucker Emily A. , Abrams Charles S. , Thompson Alexis A. , Anderson Kenneth C. , Kluetz Paul , Farrell Ann , Rivera Donna , Gertzog Matthew , Pappas Gregory
Published: October 2021

The ASH Research Collaborative is a nonprofit organization established through the American Society of Hematology’s commitment to patients with hematologic conditions and the science that informs clinical care and future therapies. The ASH Research Collaborative houses 2 major initiatives: (1) the Data Hub and (2) the Clinical Trials Network (CTN). The Data Hub is a program for hematologic diseases in which networks of clinical care delivery sites are developed in specific disease areas, with individual patient data contributed through electronic health record (EHR) integration, direct data entry through electronic data capture, and external data sources. Disease-specific data models are constructed so that data can be assembled into analytic datasets and used to enhance clinical care through dashboards and other mechanisms. Initial models have been built in multiple myeloma (MM) and sickle cell disease (SCD) using the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) and Fast Healthcare Interoperability Resources (FHIR) standards. The Data Hub also provides a framework for development of disease-specific learning communities (LC) and testing of health care delivery strategies. The ASH Research Collaborative SCD CTN is a clinical trials accelerator that creates efficiencies in the execution of multicenter clinical trials and has been initially developed for SCD. Both components are operational, with the Data Hub actively aggregating source data and the SCD CTN reviewing study candidates. This manuscript describes processes involved in developing core features of the ASH Research Collaborative to inform the stakeholder community in preparation for expansion to additional disease areas.
A novel NUP98-JADE2 fusion in a patient with acute myeloid leukemia resembling acute promyelocytic leukemia
Authors: Cheng Chi-Keung , Chan Hoi-Yun , Yung Yuk-Lin , Wan Thomas S. K. , Leung Alex W. K. , Li Chi-Kong , Tian Ke , Chan Natalie P. H. , Cheung Joyce S. , Ng Margaret H. L.
Published: October 2021

Acute promyelocytic leukemia (APL) is a specific subtype of acute myeloid leukemia (AML) characterized by block of differentiation at the promyelocytic stage and the presence of PML-RARA fusion. In rare instances, RARA is fused with other partners in variant APL. More infrequently, non-RARA genes are rearranged in AML patients resembling APL. However, the underlying disease pathogenesis in these atypical cases is largely unknown. Here, we report the identification and characterization of a NUP98- JADE2 fusion in a pediatric AML patient showing APL-like morphology and immunophenotype. Mechanistically, we showed that NUP98-JADE2 could impair all-trans retinoic acid (ATRA)-mediated transcriptional control and myeloid differentiation. Intriguingly, NUP98-JADE2 was found to alter the subcellular distribution of wild-type JADE2, whose down-regulation similarly led to attenuated ATRA-induced responses and myeloid activation, suggesting that NUP98-JADE2 may mediate JADE2 inhibition. To our knowledge, this is the first report of a NUP98-non-RAR rearrangement identified in an AML patient mimicking APL. Our findings suggest JADE2 as a novel myeloid player involved in retinoic acid-induced differentiation. Despite lacking a rearranged RARA, our findings implicate that altered retinoic acid signaling by JADE2 disruption may underlie the APL-like features in our case, corroborating the importance of this signaling in APL pathogenesis.
Heterogeneity of treatment response in bronchiectasis clinical trials
Authors: Sibila Oriol , Laserna Elena , Shoemark Amelia , Perea Lidia , Bilton Diana , Crichton Megan L. , De Soyza Anthony , Boersma Wim G. , Altenburg Josje , Chalmers James D.
Published: October 2021

Background

Recent randomised clinical trials in bronchiectasis have failed to reach their primary end-points, suggesting a need to reassess how we measure treatment response. Exacerbations, quality of life (QoL) and lung function are the most common end-points evaluated in bronchiectasis clinical trials. We aimed to determine the relationship between responses in terms of reduced exacerbations, improved symptoms and lung function in bronchiectasis.

Methods

We evaluated treatment response in three randomised clinical trials that evaluated mucoactive therapy (inhaled mannitol), an oral anti-inflammatory/antibiotic (azithromycin) and an inhaled antibiotic (aztreonam). Treatment response was defined by an absence of exacerbations during follow-up, an improvement of QoL above the minimum clinically important difference and an improvement in forced expiratory volume in 1 s (FEV1) of ≥100 mL from baseline.

Results

Cumulatively the three trials included 984 patients. Changes in FEV1, QoL and exacerbations were heterogeneous in all trials analysed. Improvements in QoL were not correlated to changes in FEV1in the azithromycin and aztreonam trials (r= −0.17, p=0.1 and r=0.04, p=0.4, respectively) and weakly correlated in the mannitol trial (r=0.22, p<0.0001). An important placebo effect was observed in all trials, especially regarding improvements in QoL. Clinical meaningful lung function improvements were rare across all trials evaluated, suggesting that FEV1is not a responsive measure in bronchiectasis.

Conclusions

Improvements in lung function, symptoms and exacerbation frequency are dissociated in bronchiectasis. FEV1is poorly responsive and poorly correlated with other key outcome measures. Clinical parameters are poorly predictive of treatment response, suggesting the need to develop biomarkers to identify responders.
Long-term outcomes of adult pulmonary Langerhans cell histiocytosis: a prospective cohort
Authors: Benattia Amira , Bugnet Emmanuelle , Walter-Petrich Anouk , de Margerie-Mellon Constance , Meignin Véronique , Seguin-Givelet Agathe , Lorillon Gwenaël , Chevret Sylvie , Tazi Abdellatif
Published: October 2021

Background

The long-term outcomes of adult pulmonary Langerhans cell histiocytosis (PLCH), particularly survival, are largely unknown. Two earlier retrospective studies reported a high rate of mortality, which contrasts with our clinical experience.

Methods

To address this issue, all patients with newly diagnosed PLCH referred to the French national reference centre for histiocytoses between 2004 and 2018 were eligible for inclusion. The primary outcome was survival, which was defined as the time from inclusion to lung transplantation or death from any cause. Secondary outcomes included the cumulative incidences of chronic respiratory failure (CRF), pulmonary hypertension (PH), malignant diseases and extrapulmonary involvement in initially isolated PLCH. Survival was estimated using the Kaplan–Meier method.

Results

206 patients (mean age 39±13 years, 60% female, 95% current smokers) were prospectively followed for a median duration of 5.1 years (IQR 3.2–7.6 years). Of these, 12 patients (6%) died. The estimated rate of survival at 10 years was 93% (95% CI 89–97%). The cumulative incidences of CRF and/or PH were <5% at both 5 and 10 years, and 58% of these patients died. 27 malignancies were observed in 23 patients. The estimated standardised incidence ratio of lung carcinoma was 17.0 (95% CI 7.45–38.7) compared to an age- and sex-matched French population. Eight (5.1%) of the 157 patients with isolated PLCH developed extrapulmonary involvement.

Conclusion

The long-term prognosis of PLCH is significantly more favourable than has previously been reported. Patients must be closely monitored after diagnosis to detect severe complications early.
Biomarker signatures for progressive idiopathic pulmonary fibrosis
Authors: Clynick Britt , Corte Tamera J. , Jo Helen E. , Stewart Iain , Glaspole Ian N. , Grainge Christopher , Maher Toby M. , Navaratnam Vidya , Hubbard Richard , Hopkins Peter M.A. , Reynolds Paul N. , Chapman Sally , Zappala Christopher , Keir Gregory J. , Cooper Wendy A. , Mahar Annabelle M. , Ellis Samantha , Goh Nicole S. , De Jong Emma , Cha Lilian , Tan Dino B.A. , Leigh Lucy , Oldmeadow Christopher , Walters E. Haydn , Jenkins R. Gisli , Moodley Yuben
Published: October 2021

Background

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease in which circulatory biomarkers have the potential for guiding management in clinical practice. We assessed the prognostic role of serum biomarkers in three independent IPF cohorts: Australian Idiopathic Pulmonary Fibrosis Registry (AIPFR), Trent Lung Fibrosis (TLF) and Prospective Observation of Fibrosis in the Lung Clinical Endpoints (PROFILE).

Methods

In the AIPFR cohort, candidate proteins were assessed by ELISA as well as in an unbiased proteomic approach. LASSO (least absolute shrinkage and selection operator) regression was used to restrict the selection of markers that best accounted for the progressor phenotype at 1 year in the AIPFR cohort, and subsequently prospectively selected for replication in the validation TLF cohort and assessed retrospectively in the PROFILE cohort. Four significantly replicating biomarkers were aggregated into a progression index model based on tertiles of circulating concentrations.

Results

189 participants were included in the AIPFR cohort, 205 participants from the TLF cohort and 122 participants from the PROFILE cohort. Differential biomarker expression was observed by ELISA and replicated for osteopontin, matrix metallopeptidase-7, intercellular adhesion molecule-1 and periostin for those with a progressor phenotype at 1 year. Proteomic data did not replicate. The progression index in the AIPFR, TLF and PROFILE cohorts predicted risk of progression, mortality and progression-free survival. A statistical model incorporating the progression index demonstrated the capacity to distinguish disease progression at 12 months, which was increased beyond the clinical GAP (gender, age and physiology) score model alone in all cohorts, and significantly so within the incidence-based TLF and PROFILE cohorts.

Conclusion

A panel of circulatory biomarkers can provide potentially valuable clinical assistance in the prognosis of IPF patients.
Mortality trends in pulmonary arterial hypertension in Canada: a temporal analysis of survival per ESC/ERS guideline era
Authors: Zelt Jason G.E. , Sugarman Jordan , Weatherald Jason , Partridge Arun C.R. , Liang Jiaming (Calvin) , Swiston John , Brunner Nathan , Chandy George , Stewart Duncan J. , Contreras-Dominguez Vladimir , Thakrar Mitesh , Helmersen Doug , Varughese Rhea , Hirani Naushad , Umar Fraz , Dunne Rosemary , Doyle-Cox Caroyln , Foxall Julia , Mielniczuk Lisa
Published: October 2021

Background

The evolution in pulmonary arterial hypertension (PAH) management has been summarised in three iterations of the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines. No study has assessed whether changes in management, as reflected in the changing guidelines, has translated to improved long-term survival in PAH.

Methods

We performed a mixed retrospective/prospective analysis of treatment-naïve, incident PAH patients (n=392) diagnosed at three major centres in Canada from 2009 to 2021. Patients were divided into two groups based on their diagnosis date and in accordance with the 2009 and 2015 ESC/ERS guideline iterations. Overall survival was assessed based on date of diagnosis and initial treatment strategy (i.e.monotherapyversuscombination therapy).

Results

There was a shift towards more aggressive upfront management with combination therapy in Canada after the publication of the 2015 ESC/ERS guidelines (10.4% and 30.8% in patients from 2009 to 2015 and 36.0% and 57.4% in patients diagnosed after 2015 for baseline and 2-year follow-up, respectively). A key factor associated with combination therapy after 2015 was higher pulmonary vascular resistance (p=0.009). The 1-, 3- and 5-year survival rates in Canada were 89.2%, 75.6% and 56.0%, respectively. Despite changes in management, there was no improvement in long-term survival before and after publication of the 2015 ESC/ERS guidelines (p=0.53).

Conclusions

There was an increase in the use of initial and sequential combination therapy in Canada after publication of the 2015 ESC/ERS guidelines, which was not associated with improved long-term survival. These data highlight the continued difficulties of managing this aggressive pulmonary disease in an era without a cure.
Profiling of lung SARS-CoV-2 and influenza virus infection dissects virus-specific host responses and gene signatures
Authors: Kulasinghe Arutha , Tan Chin Wee , Ribeiro dos Santos Miggiolaro Anna Flavia , Monkman James , SadeghiRad Habib , Bhuva Dharmesh D. , Motta Junior Jarbas da Silva , Busatta Vaz de Paula Caroline , Nagashima Seigo , Baena Cristina Pellegrino , Souza-Fonseca-Guimaraes Paulo , de Noronha Lucia , McCulloch Timothy , Rossi Gustavo Rodrigues , Cooper Caroline , Tang Benjamin , Short Kirsty R. , Davis Melissa J. , Souza-Fonseca-Guimaraes Fernando , Belz Gabrielle T. , O'Byrne Ken
Published: October 2021

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged in late 2019 has spread globally, causing a pandemic of respiratory illness designated coronavirus disease 2019 (COVID-19). A better definition of the pulmonary host response to SARS-CoV-2 infection is required to understand viral pathogenesis and to validate putative COVID-19 biomarkers that have been proposed in clinical studies.

Methods

Here, we use targeted transcriptomics of formalin-fixed paraffin-embedded tissue using the NanoString GeoMX platform to generate an in-depth picture of the pulmonary transcriptional landscape of COVID-19, pandemic H1N1 influenza and uninfected control patients.

Results

Host transcriptomics showed a significant upregulation of genes associated with inflammation, type I interferon production, coagulation and angiogenesis in the lungs of COVID-19 patients compared to non-infected controls. SARS-CoV-2 was non-uniformly distributed in lungs (emphasising the advantages of spatial transcriptomics) with the areas of high viral load associated with an increased type I interferon response. Once the dominant cell type present in the sample, within patient correlations and patient–patient variation, had been controlled for, only a very limited number of genes were differentially expressed between the lungs of fatal influenza and COVID-19 patients. Strikingly, the interferon-associated geneIFI27, previously identified as a useful blood biomarker to differentiate bacterial and viral lung infections, was significantly upregulated in the lungs of COVID-19 patients compared to patients with influenza.

Conclusion

Collectively, these data demonstrate that spatial transcriptomics is a powerful tool to identify novel gene signatures within tissues, offering new insights into the pathogenesis of SARS-COV-2 to aid in patient triage and treatment.
Temporal trends in pulmonary arterial hypertension: results from the COMPERA registry
Authors: Hoeper Marius M. , Pausch Christine , Grünig Ekkehard , Staehler Gerd , Huscher Doerte , Pittrow David , Olsson Karen M. , Vizza Carmine Dario , Gall Henning , Distler Oliver , Opitz Christian , Gibbs J. Simon R. , Delcroix Marion , Ghofrani H. Ardeschir , Rosenkranz Stephan , Park Da-Hee , Ewert Ralf , Kaemmerer Harald , Lange Tobias J. , Kabitz Hans-Joachim , Skowasch Dirk , Skride Andris , Claussen Martin , Behr Juergen , Milger Katrin , Halank Michael , Wilkens Heinrike , Seyfarth Hans-Jürgen , Held Matthias , Dumitrescu Daniel , Tsangaris Iraklis , Vonk-Noordegraaf Anton , Ulrich Silvia , Klose Hans
Published: October 2021

Background

Since 2015, the European pulmonary hypertension guidelines recommend the use of combination therapy in most patients with pulmonary arterial hypertension (PAH). However, it is unclear to what extent this treatment strategy is adopted in clinical practice and if it is associated with improved long-term survival.

Methods

We analysed data from COMPERA, a large European pulmonary hypertension registry, to assess temporal trends in the use of combination therapy and survival of patients with newly diagnosed PAH between 2010 and 2019. For survival analyses, we looked at annualised data and at cumulated data comparing the periods 2010–2014 and 2015–2019.

Results

A total of 2531 patients were included. The use of early combination therapy (within 3 months after diagnosis) increased from 10.0% in patients diagnosed with PAH in 2010 to 25.0% in patients diagnosed with PAH in 2019. The proportion of patients receiving combination therapy 1 year after diagnosis increased from 27.7% to 46.3%. When comparing the 2010–2014 and 2015–2019 periods, 1-year survival estimates were similar (89.0% (95% CI 87.2–90.9%) and 90.8% (95% CI 89.3–92.4%), respectively), whereas there was a slight but nonsignificant improvement in 3-year survival estimates (67.8% (95% CI 65.0–70.8%) and 70.5% (95% CI 67.8–73.4%), respectively).

Conclusions

The use of combination therapy increased from 2010 to 2019, but most patients still received monotherapy. Survival rates at 1 year after diagnosis did not change over time. Future studies need to determine if the observed trend suggesting improved 3-year survival rates can be confirmed.
Pilot study on nocturnal monitoring of crackles in children with pneumonia
Authors: Nikolaizik Wilfried , Wuensch Lisa , Bauck Monika , Gross Volker , Sohrabi Keywan , Weissflog Andreas , Hildebrandt Olaf , Koehler Ulrich , Weber Stefanie
Published: October 2021

Background

The clinical diagnosis of pneumonia is usually based on crackles at auscultation, but it is not yet clear what kind of crackles are the characteristic features of pneumonia in children. Lung sound monitoring can be used as a “longtime stethoscope”. Therefore, it was the aim of this pilot study to use a lung sound monitor system to detect crackles and to differentiate between fine and coarse crackles in children with acute pneumonia. The change of crackles during the course of the disease shall be investigated in a follow-up study.

Patients and methods

Crackles were recorded overnight from 22:00 to 06:00 h in 30 children with radiographically confirmed pneumonia. The data for a total of 28 800 recorded 30-s epochs were audiovisually analysed for fine and coarse crackles.

Results

Fine crackles and coarse crackles were recognised in every patient with pneumonia, but the number of epochs with and without crackles varied widely among the different patients: fine crackles were detected in 40±22% (mean±sd), coarse crackles in 76±20%. The predominant localisation of crackles as recorded during overnight monitoring was in accordance with the radiographic infiltrates and the classical auscultation in most patients. The distribution of crackles was fairly equal throughout the night. However, there were time periods without any crackle in the single patients so that the diagnosis of pneumonia might be missed at sporadic auscultation.

Conclusion

Nocturnal monitoring can be beneficial to reliably detect fine and coarse crackles in children with pneumonia.
Lung cancer mortality in Europe and the USA between 2000 and 2017: an observational analysis
Authors: Jani Chinmay , Marshall Dominic C. , Singh Harpreet , Goodall Richard , Shalhoub Joseph , Al Omari Omar , Salciccioli Justin D. , Thomson Carey C.
Published: October 2021

Background

The lung is the most common site for cancer and has the highest worldwide cancer-related mortality. Our study reports and compares trends in lung cancer mortality in the USA and 26 European countries.

Study design and methods

Lung cancer mortality data were extracted for males and females for each of the years 2000–2017 from the World Health Organization (WHO) Mortality and the Centers for Disease Control and Prevention (CDC) WONDER databases. Lung cancer mortality trends were compared using Joinpoint regression analysis, and male-to-female mortality ratios were calculated.

Results

Down-trending lung cancer mortality rates were observed in males in all countries except Cyprus and Portugal between 2000 and 2017. In females, increasing mortality rates were observed in 22 of the 27 countries analysed. Latvia had the highest estimated annual percentage change (EAPC) in male mortality (−9.6%) between 2013 and 2015. In the USA, EAPCs were −5.1% for males and −4.2% for females between 2014 and 2017. All countries had an overall decrease in the ratio of male-to-female lung cancer mortality. The most recent observation of median male-to-female mortality was 2.26 (IQR 1.92–4.05). The countries with the greatest current sex disparity in lung cancer mortality were Lithuania (5.51) and Latvia (5.00).

Conclusion

Between 2000 and 2017, lung cancer mortality rates were decreasing for males in Europe and the USA, whereas increasing lung cancer mortality rates were generally observed in females. There is a persistent but decreasing sex-mortality gap, with men having persistently greater lung cancer mortality but with rates decreasing faster than women.