bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceptual constancy and perceptual representation
Authors: Green E. J.
Published: March 2023

Perceptual constancy has played a significant role in philosophy of perception. It figures in debates about direct realism, color ontology, and the minimal conditions for perceptual representation. Despite this, there is no general consensus about what constancy is. I argue that an adequate account of constancy must distinguish it from three distinct phenomena: mere sensory stability through proximal change, perceptual categorization of a distal dimension, and stability through irrelevant proximal change. Standard characterizations of constancy fall short in one or more of these respects. I develop an account of constancy that overcomes these problems. The account has two parts: an analysis of constancy mechanisms, and an analysis of the conditions under which a constancy capacity is exercised. I then employ this account to evaluate whether constancy is a necessary condition for perceptual representation, as some have conjectured. I argue that explanatory practice in perceptual psychology fails to support this view. Rather, it fits better with the weaker principle that representation requires specific tracking of a distal dimension.
The categorical paradoxes in the sharing economy: Empirical evidence from Airbnb
Authors: Huang Yuxin , Shen Yi , Lai Fujun , Luo Xin (Robert)
Published: March 2023

Challenging conventional epistemological stances, we unravel two paradoxes of communication strategies in the emerging context of sharing economy. Specifically, the conformity–distinctiveness paradox asserts that differing from hotels improves hosts’ economic performance, but such economic benefit diminishes when deviating from the norms in hospitality settings. The economic–social paradox propounds that positioning away from hotels improves social performance but may not result in optimal economic gains. Drawing on the theoretical underpinnings of strategic categorization and optimal distinctiveness, we collect and analyze data from a sample of Airbnb listings. Utilizing multiple estimation models and identification strategies, we find that hosts can improve their economic performance by differing from hotels, but such economic gains diminish beyond a certain point. Furthermore, deviating from hotels also increases hosts’ social performance, especially when direct host–guest interactions occur in shared apartments. Our empirical findings provide compelling evidence for the two paradoxes in the context of sharing economy, extend the discourse on strategic categorization, and elucidate the effects of listing narratives conveyed through social technologies. This study also sheds new light on how operations management and service providers can exploit the communicative and linguistic perspectives of user‐generated content.
Mandatory due diligence laws and climate change litigation: Bridging the corporate climate accountability gap?
Authors: Rajavuori Mikko , Savaresi Annalisa , van Asselt Harro
Published: March 2023

The debate on corporate climate accountability has become increasingly prominent in recent years. Several countries, particularly in the Global North, have adopted mandatory human rights and/or environmental due diligence legislation. At the same time, judicial and quasi‐judicial proceedings are helping to shape the contours of corporate climate accountability. This article considers how litigation against corporations and due diligence legislation interact, and thereby help develop and strengthen corporate climate accountability. While the practice in this area is still limited, there is scope to reflect on early developments and how they may influence both future climate litigation as well as ongoing and future law‐making on due diligence. We first review recent developments in climate litigation against corporations, focusing on the extent to which they rely on climate due diligence obligations. We then survey existing and proposed due diligence legislation, examining the extent to which it addresses corporate climate accountability. Finally, we identify scenarios of how due diligence legislation and climate litigation may interact and possibly converge to strengthen corporate climate accountability. We furthermore identify knowledge gaps and areas for further research.
Outside the borders of the state, abandonment. On the new forms of disappearance
Authors: Gatti Gabriel
Published: March 2023

In this article I propose an expanded definition of the categories of “disappearance” and “disappeared” with which to address situations marked by abandonment. In the first movement, I provide a critical description of the scientific literature available about disappearance in several fields, in particular legal and political sociology. Both have gradually constructed an interpretation that, while legally effective, sociologically sensitive, and socially successful, currently find themselves overwhelmed. The second movement confirms that the dominant meaning of disappearance and disappeared has been overwhelmed, and it addresses how that overwhelming affects three of their characteristics: the timeframes of reference for both categories (the past and memory); the anthropological assumptions that underpin the two (the bad death and the (im)possibility of its conventional management); and the normative social frameworks that both take as “a given” (the state and citizenship, and the forms of political agency associated with them). Finally, the third movement deals with different experiences of field research related to very open uses of the idea of disappearance, to gather different efforts of theoretical problematization that currently, and in various fields of social science research, turn disappearance and disappeared into tools for analyzing social forms of abandonment.
“Racial Heterosexual Habitus” and Management of Racial Education Discussions Within Black Female/White Male Romantic Relationships1
Authors: Mtshali Marya Thembi
Published: March 2023

Scholars (Steinbugler 2012; Twine 2010) have examined the role that the white racial lens can play in limiting the development of racial literacy for white partners in black/white relationships, while the role of gender ideologies has gone largely unexamined. Through analyzing “racially educational” conversations between 36 members of black female/white male heterosexual couples, I introduce the concept of “racial heterosexual habitus” and its influence in managing these discussions on race. I argue that it generates limits—as well as unique opportunities—for couples during these conversations about race. My findings reveal how black female heterosexual habitus orients black women to navigate these conversations by looking to black femininity to advocate against their partner's racism and sexism and to also determine the conceptual limit of these conversations in deference to protecting white masculinity. However, contrary to understandings of black middle‐class femininity, women in longer‐duration relationships advocated for themselves in defense of their partner's comments. Additionally, I show how white male heterosexual habitus limits the ability to develop racial literacy with its hegemonic masculine focus on achievement and autonomy. This work not only centers racialized gender ideologies in the study of interracial couples but also extends Bourdieu's concept of habitus.
Contrast-enhanced ultrasound demonstrates greater adjuvant potential: past, current status, and future applications in Hepatocellular carcinoma early diagnosis
Authors: Li Nana , Nie Fang , Wang Yao , Pang Wenjing , Wang Wenzhu , Zhao Yunpeng , Jia Yingying
Published: March 2023

Hepatocellular carcinoma (HCC) has an atypical onset of clinical symptoms and a rapid tumor progression. The majority of patients with HCC are already in the late stages of the disease when they are diagnosed, limiting them to the best available treatments. Contrast-enhanced ultrasound (CEUS) has achieved significant advances in the diagnosis of HCC, including the detection of small lesions, the investigation of more beneficial contrast agents, and the use of CEUS-based radiomics. The purpose of this review is to discuss the relevant research and future challenges of CEUS in the early detection of HCC, to advise more accurate therapy.
Influence of γ'N and ɛ'N phases on the properties of AISI 304L after low-temperature plasma nitrocarburizing
Authors: Sah Jeet Vijay , Dwivedi Pravin Kumari , Mukherjee Subroto , Jhala Ghanshyam , Joseph Alphonsa
Published: March 2023

The surface of austenitic stainless steel AISI 304L has been hardened by adding nitrogen and carbon through the plasma nitrocarburizing process. Plasma nitrocarburizing at low temperatures eliminates the formation of nitrides and carbides of chromium, thereby increasing the surface hardness without compromising its corrosion resistance. This is attributed to the presence of a hard case consisting of a solid-solution of nitrogen and carbon occupying interstitial sites in an “expanded” austenite phase. The expanded austenite is further characterized as nitrogen-expanded austenite (γN) and carbon-expanded austenite (γC). In the present work, austenitic stainless steel AISI 304L samples were plasma nitrocarburized by varying the N2 content (%N2) in N2-H2-C2H2 feed gas mixture and treatment times (3, 5, and 7 h) at 673 K and 500 Pa. The samples were characterized by means of XRD, microindentation, XPS, EIS, and potentiodynamic polarization testing, for studying the microstructural, mechanical, and electrochemical properties. The XRD analysis revealed the presence of ɛ'N and γ'N in addition to γN and γC when treated with higher %N2 gas for 5 and 7 h. From XPS, the binding energies of undefined FexN were obtained which were found to lie very close to the defined FexN for higher %N2 gas. Surface hardness significantly improved after the plasma nitrocarburizing processes irrespective of the %N2 and treatment times compared to the untreated AISI 304L. The presence of CrN precipitation on the surface of samples treated with the 75% N2 for 5 and 7 h were observed from XPS, which caused higher corrosion rate. Among the treated samples, the process with 50% N2 and 5 h exhibited the best corrosion resistance with high surface hardness.
Link between cracking mechanisms of trilayer films on flexible substrates and electro-mechanical reliability under biaxial loading
Authors: Altaf Husain S. , Kreiml P. , Renault P.-O. , Mitterer C. , Cordill M. J. , Faurie D.
Published: March 2023

The propagation of cracks from a top layer in trilayer systems (Cr/Cu/Mo) on a polyimide substrate is studied experimentally by in situ synchrotron x-ray diffraction under equi-biaxial loading. The results show that depending on the thickness of the ductile Cu middle layer (100 or 500 nm), the propagation can be a direct vertical path through all layers or a more complex path. These effects are analyzed by monitoring the individual stresses of each layer along with electrical resistance and resulting crack patterns. Cracks starting from the upper Cr layer propagate instantaneously through the whole system for a 100 nm Cu layer but are strongly deflected in a 500 nm Cu layer, thus delaying the global fracture of the system measured by the increase of electrical resistance. Mechanisms are proposed and allowed to anticipate the electro-mechanical performances of stretchable systems constructed of several layers.
Effects of the temperature of a protic ionic liquid on ion beam production by vacuum electrospray
Authors: Fujiwara Yukio
Published: March 2023

Ionic liquid ion sources generate ion beams from ionic liquids by vacuum electrospray. Electrospray characteristics generally depend on the physical properties of the liquids used. A key factor affecting physical properties is temperature. In this study, ion beam production was investigated using a protic ionic liquid, propylammonium nitrate (PAN), at temperatures ranging from 22 to 60 °C. An ion beam was produced using a needle emitter equipped with a cartridge heater, thermocouple, and sharpened glass rod externally wetted with PAN. The experimental results showed that the heating of the emitter increased the ion beam current. This will be due to an increase in the conductivity and a decrease in the viscosity of PAN with increasing temperature. Furthermore, the abundance of larger cluster ions increased, whereas that of smaller cluster ions decreased with increasing temperature. It turned out, however, that higher heating of the emitter stopped ion beam production. Two hypotheses for the beam stop are proposed and discussed.
Patterns of Physical Activity and Sedentary Behavior During the COVID-19 Pandemic in the Thai 2021 National Health Survey
Authors: Topothai Thitikorn , Tangcharoensathien Viroj , Suphanchaimat Rapeepong , Petrunoff Nicholas Alexander , Chandrasiri Orana , Müller-Riemenschneider Falk
Published: March 2023

Background: Understanding patterns of physical activity and sedentary behavior is essential, but evidence from low- and middle-income countries remains limited. This study aimed to investigate the prevalence of physical activity and sedentary behavior in the Thai population; their sociodemographic correlates; and the contribution of specific domains to total physical activity. Methods: We analyzed data from the 2021 Health Behavior Survey, a nationally representative survey, conducted by the Thailand National Statistical Office during the COVID-19 pandemic. Physical activity and sedentary behavior were assessed using the Global Physical Activity Questionnaire. “Sufficiently active” was defined according to the World Health Organization guidelines. “Highly sedentary” was defined as sitting ≥7 hours per day. The contribution of work, transport, and recreational physical activity was determined as the proportion of total physical activity. Multivariable logistic regression was conducted to determine the correlates of being sufficiently active and being highly sedentary. Results: Of the total study population (N = 78,717), 71.9% were sufficiently active, whereas 75.8% were highly sedentary. Females, having a labor-intensive work, and living in Bangkok had a higher likelihood of being sufficiently active. Those with higher education and income levels, and living in Bangkok and the Central region had a greater likelihood of being highly sedentary. The work domain contributed the highest proportion toward physical activity (82.1%), followed by the recreation (10.0%) and transport domains (7.9%). Conclusions: Policies should focus on promoting transport and recreational physical activity and activity that can break up sedentary behavior among adults because when countries become technologically advanced, physical activity at work declines.
Molluscum Contagiosum Virus Protein MC008 Targets NF-κB Activation by Inhibiting Ubiquitination of NEMO
Authors: Phelan Thomas , Lawler Clara , Pichlmair Andreas , Little Mark A. , Bowie Andrew G. , Brady Gareth
Published: March 2023

Inflammation lies at the heart of most human diseases. Understanding the pathways that drive this response is the key to new anti-inflammatory therapies.
UHRF1 Deficiency Inhibits Alphaherpesvirus through Inducing RIG-I-IRF3-Mediated Interferon Production
Authors: Wang Mengdong , Song Jingjing , Gao Chao , Yu Cuilian , Qin Chao , Lang Yue , Xu Aotian , Liu Yun , Feng Wenhai , Tang Jun , Zhang Rui
Published: March 2023

Alphaherpesviruses can establish lifelong infections and cause many diseases in humans and animals, which rely partly on their interaction with IFN-mediated innate immune response. Using alphaherpesviruses PRV and HSV-1 as models, we identified an essential role of DNA methylation regulator UHRF1 in IFN-mediated immunity against virus replication, which unravels a novel mechanism employed by epigenetic factor to control IFN-mediated antiviral immune response and highlight UHRF1, which might be a potential target for antiviral drug development.
The Genetic Variation of Porcine Reproductive and Respiratory Syndrome Virus Replicase Protein nsp2 Modulates Viral Virulence and Persistence
Authors: Kong Can , Li Dan , Hu Yanxin , Gao Peng , Zhang Yongning , Zhou Lei , Ge Xinna , Guo Xin , Han Jun , Yang Hanchun
Published: March 2023

Porcine reproductive and respiratory syndrome virus (PRRSV) has been a major threat to the world swine industry. In the field, rapid genetic variations (e.g., deletion, mutation, recombination, etc.) within the nsp2 region present an intriguing conundrum to PRRSV biology and pathogenesis.
Knockdown Experiment Reveals an Essential GTPase CgtA’s Involvement in Growth, Viability, Motility, Morphology, and Persister Phenotypes in Vibrio cholerae
Authors: Das Sagarika , Chatterjee Ananya , Datta Partha Pratim
Published: March 2023

It is very important that we must find new drug target proteins from multidrug-resistant human-pathogenic organisms like
V. cholerae
. CgtA is among such potential candidates, and here, we are reporting about some newly identified cellular roles of it that are important for the survival of
V. cholerae
.
Mycorrhizae Enhance Soybean Plant Growth and Aluminum Stress Tolerance by Shaping the Microbiome Assembly in an Acidic Soil
Authors: Wen Zhongling , Yang Minkai , Han Hongwei , Fazal Aliya , Liao Yonghui , Ren Ran , Yin Tongming , Qi Jinliang , Sun Shucun , Lu Guihua , Hu Shuijin , Yang Yonghua
Published: March 2023

Taken together, this study examined the effects of arbuscular mycorrhizal fungi (AMF) and rhizobial combinations on the growth of Al-tolerant and Al-sensitive soybeans as well as their associated microbial communities in acidic soils and concluded that AMF enhances soybean growth and Al stress tolerance by recruiting PGPR and altering the root-associated microbiome assembly in a host-dependent manner. In the future, these findings will help us better understand the impacts of AMF on rhizosphere microbiome assembly and will contribute to the development of soybean breeding techniques for the comprehensive use of PGPR in sustainable agriculture.
Conserved Expression and Functionality of Furin between Chickens and Ducks as an Activating Protease of Highly Pathogenic Avian Influenza Virus Hemagglutinins
Authors: de Bruin Anja C. M. , Spronken Monique I. , Bestebroer Theo M. , Fouchier Ron A. M. , Richard Mathilde
Published: March 2023

HPAIV outbreaks are a global concern due to the health risks for poultry, wildlife, and humans and their major economic impact. The number of LPAIV-to-HPAIV conversions, which is associated with spillover from wild birds to poultry, has been increasing over recent decades.
Transformation of Compatible Mating-Type Genes in Monokaryons Triggers Fruiting Body Development by Activating Mating Pathways in
Pleurotus eryngii
Authors: Shang Junjun , Xu Sijia , Tang Lihua , Yang Ruiheng , Gong Ming , Li Yan , Wang Ying , Zou Gen , Wan Jianing , Bao Dapeng
Published: March 2023

Fruiting bodies of edible mushrooms have high nutritional value. However, the fruiting body development of mushrooms is not well understood, and thus, many wild edible mushrooms of economic importance cannot be cultivated artificially.
Fragility fractures and reversible osteopaenia due to chronic hyponatraemia in an adolescent male
Authors: Patel Mital , Ayus Juan Carlos , Moritz Michael L
Published: March 2023

Fragility fractures are common in older adults and rare in children. Recent studies have demonstrated that hyponatraemia is a novel risk factor for the development of osteoporosis and hip fractures in older people. Animal studies suggest that hyponatraemia can lead to decreased bone mineral density by stimulating osteoclastic activity in order to mobilise sodium from the bone. Reported is a 16-year-old man with intractable epilepsy and an 11-year history of chronic hyponatraemia (126–135 mEq/L) due to valproic acid induced syndrome of inappropriate antidiuresis who sustained low-impact fragility fractures and had evidence of osteopaenia on both X-ray and dual energy X-ray absorptiometry (DEXA). Hyponatraemia resolved following the discontinuation of valproic acid and bone mineral density normalised on a repeat DEXA 19 months later. This case provides evidence supporting the contention that chronic hyponatraemia contributes to osteopaenia and fragility fractures and that the bone abnormalities are potentially reversible following the correction of hyponatraemia.
Early retinal neurovascular impairment in patients with diabetes without clinically detectable retinopathy
Authors: Zeng Yunkao , Cao Dan , Yu Honghua , Yang Dawei , Zhuang Xuenan , Hu Yunyan , Li Juan , Yang Jing , Wu Qiaowei , Liu Baoyi , Zhang Liang
Published: March 2023

Aims

To investigate the function and the corresponding neurovascular structures in patients with diabetes without clinically detectable retinopathy.

Methods 

Sixty-six patients with type 2 diabetes without retinopathy (NDR) and 62 healthy controls were recruited. The 16 and 32 Tds flicker electroretinography (ERG) was performed using a mydriasis-free, full-field flicker ERG recording device (RETeval). The vessel density (VD) of superficial capillary plexus (SCP) and deep capillary plexus (DCP), FD300 and ganglion cell complex (GCC) thickness in the macula were quantified using optical coherence tomography angiography (OCTA). The retinal nerve fibre layer (RNFL) thickness and the radial peripapillary capillary (RPC) density in the peripapillary area were also measured with OCTA.

Results

Parafoveal and perifoveal VD in both SCP and DCP decreased in NDR group in comparison to control group (all p<0.01). However, macular GCC thickness was comparable between the two groups (p=0.661). Peripapillary RNFL thickness and RPC density were significantly lower in NDR group (p<0.001 and p=0.009, respectively). With regard to ERG parameters, delayed implicit time and decreased amplitude were found in NDR group in comparison to the control group (all p<0.01). In the multiple linear regression analyses, delayed implicit time for 16 and 32 Tds stimuli was significantly correlated with increased HbA1c (β=0.350, p<0.001; β=0.328, p<0.001, respectively) and decreased VD of SCP in the parafoveal region (β=−0.266, p=0.013; β=−0.253, p=0.005, respectively). However, delayed implicit time for 16 and 32 Tds stimuli was not correlated with the thickness of GCC (β=−0.008, p=0.818) in multiple linear regression analyses.

Conclusion

Functional and structural impairments have already started in diabetic retina even in the absence of visible retinal lesions. Subtle microvascular abnormalities rather than ganglion cell loss might be associated with early functional changes in NDR patients. Poor control of blood glucose was associated with delayed implicit time of flicker ERG in preclinical diabetic retinopathy.
Causes of diabetic ketoacidosis among adults with type 1 diabetes mellitus: insulin pump users and non-users
Authors: Flores Monica , Amir Maryam , Ahmed Ramsha , Alashi Suleiman , Li Manshi , Wang Xiaofeng , Lansang M Cecilia , Al-Jaghbeer Mohammed J
Published: March 2023

Introduction

Insulin pumps are increasingly being used as a method of insulin delivery in patients with type 1 diabetes mellitus (T1DM). Diabetic ketoacidosis (DKA) is a serious complication of T1DM. This study aims to identify the causes of DKA in patients with T1DM on continuous subcutaneous insulin infusion (CSII) and to compare these with patients with T1DM on multiple daily insulin injections (MDIIs).

Research design and methods

This is a prospective observational study between January and June 2019 at the Cleveland Clinic Fairview Hospital. Demographic, clinical, and biochemical data were obtained from chart review. A questionnaire to explore additional clinical data relating to DKA was administered, with additional items for patients on the insulin pump.

Results

Seventy-four patients were admitted with a diagnosis of DKA between the period of January and June 2019. Of these, 45 met the inclusion criteria and 43 consented. These were divided into two groups: group 1 included patients on MDII and group 2 included CSII. Overall, the most common precipitating factor for developing DKA was insulin non-adherence, seen in 51.2% of the cases. The most common cause of DKA in group 2 was pump/tubing related to 55% of the cases.

Conclusion

Despite non-adherence being common in both CSII and MDII, a combination of social factors, education and insulin pump malfunction, such as pump/tubing problems, might be playing a pivotal role in DKA etiology in young adults with T1DM, especially in CSII users. Continued education on pump use may reduce the rate of DKA in pump users.
Incidence and regression of metabolic syndrome in a representative sample of the Spanish population: results of the cohort di@bet.es study
Authors: Cuesta Martín , Fuentes Manuel , Rubio Miguel , Bordiu Elena , Barabash Ana , Garcia de la Torre Nuria , Rojo-Martinez Gemma , Valdes Sergio , Soriguer Federico , Vendrell Joan Josep , Urrutia Ines Maria , Ortega Emilio , Montanya Eduard , Menendez Eldelmiro , Lago-Sampedro Ana , Gomis Ramón , Goday Albert , Castell Conxa , Badia-Guillen Rocio , Girbés Juan , Gaztambide Sonia , Franch-Nadal Josep , Delgado Álvarez Elías , Chaves Felipe Javier , Castano Luis , Calle-Pascual Alfonso L
Published: March 2023

Introduction

Metabolic syndrome (MetS) is an important predictor of cardiovascular mortality. Identification of occurrence and regression trends of MetS could permit elaboration of preventive strategies with new targets. The objective of this study was to analyze the occurrence and regression rates of MetS and its associated factors in the representative cohort of Spain of the di@bet.es study.

Research design and methods

The di@bet.es study is a prospective cohort where 5072 people representative of the Spanish population over 18 years of age were randomly selected between 2009 and 2010. Follow-up was a median of 7.5 (IQR 7.2–7.9) years, with 2408 (47%) participating subjects. A total of 1881 (78%) subjects had all the pertinent data available and were included in this study.

Results

Of the 1146 subjects without baseline criteria for MetS, 294 (25.7%) developed MetS during follow-up, while of the 735 patients with prior MetS, 148 (20.1%) presented regression. Adjusted MetS incidence per 1000 person-years was 38 (95% CI 32 to 44), while regression incidence was 36 (95% CI 31 to 41). Regression rate was independently higher than incidence rate in the following: women, subjects aged 18–45, university-degree holders, patients without central obesity, without hypertension, as well as those with body mass index of <25 kg/m2. Lower progression and higher regression rates were observed with an adapted 14-point Mediterranean Diet adherence screener questionnaire score of >11 in both groups and with >500 and>2000 MET-min/week of physical activity, respectively.

Conclusions

This study provides MetS incidence and regression rates, and identifies the target population for intervention strategies in Spain and possibly in other countries.
Evaluating the prognostic performance of bedside tests used for peripheral arterial disease diagnosis in the prediction of diabetic foot ulcer healing
Authors: Elghazaly Hussein , Howard Theodore , Sanjay Sharan , Mohamed Omer G , Sounderajah Viknesh , Mehar Zaheer , Davies Alun H , Jaffer Usman , Normahani Pasha
Published: March 2023

Introduction

Diabetic foot ulceration (DFU) is a common and challenging complication of diabetes. Risk stratification can guide further management. We aim to evaluate the prognostic performance of bedside tests used for peripheral arterial disease (PAD) diagnosis to predict DFU healing.

Research design and methods

Testing for Arterial Disease in Diabetes (TrEAD) was a prospective observational study comparing the diagnostic performance of commonly used tests for PAD diagnosis. We performed a secondary analysis assessing whether these could predict DFU healing. Follow-up was performed prospectively for 12 months. The primary outcome was sensitivity for predicting ulcer healing. Secondary endpoints were specificity, predictive values, and likelihood ratios for ulcer healing.

Results

123 of TrEAD participants with DFU were included. In 12 months, 52.8% of ulcers healed. The best negative diagnostic likelihood ratio (NDLR) was observed for the podiatry ankle duplex scan (PAD-scan) monophasic or biphasic with adverse features(NDLR 0.35, 95% CI 0.14–0.90). The highest positive likelihood ratios were observed for toe brachial pressure index of ≤0.2 (positive diagnostic likelihood ratio (PDLR) 7.67, 95% CI 0.91–64.84) and transcutaneous pressure of oxygen of ≤20 mm Hg (PDLR 2.68, 95% CI 0.54–13.25). Cox proportional hazards modeling demonstrated significantly greater probabilities of healing with triphasic waveforms (HR=2.54, 95% CI 1.23–5.3, p=0.012) and biphasic waveforms with non-adverse features (HR=13.67, 95% CI 4.78–39.1, p<0.001) on PAD-scan.

Conclusions

No single test performed well enough to be used in isolation as a prognostic marker for the prediction of DFU healing.

Trial registration number

NCT04058626.
Job demands at the patient’s bedside and their effects on stress and satisfaction of nurses
Authors: Wenderott Katharina , Franz Shiney , Friedrich Martin G , Boos Margarete
Published: March 2023

Aim

The study aimed to assess job demands at the patient’s bedside and to evaluate the contribution of this central workplace to the stress and satisfaction of nurses.

Design

In this cross-sectional survey study, a questionnaire was compiled and all registered nurses from intensive, general and intermediate care wards at a large German hospital were invited to participate.

Methods

The questionnaire used a list of care activities to assess nurses' workload at the patient’s bed. The German Copenhagen Psychosocial Questionnaire and an adapted version of the German Perceived Stress Scale were used to measure nurses’ stress and burn-out, and single items to assess health status, organisational commitment, job satisfaction, and satisfaction with the quality of care. The questionnaire was returned by 389 nurses.

Results

Expected correlations of workload at the patient’s bed with stress, burn-out and satisfaction of the nurses were shown. A moderating effect of organisational commitment was non-existent but was shown for the self-assessed health on the correlation between workload and satisfaction with the quality of care. Organisational commitment correlated negatively with stress and burn-out and positively with satisfaction. The study provides evidence that rates of burn-out and stress do not differ based on the work area of nurses. Because job demands at the patient’s bed correlated with all outcomes, measures to improve this specific workspace are sensible.
Healthcare cost burden of acute chest pain presentations
Authors: Dawson Luke , Nehme Emily , Nehme Ziad , Zomer Ella , Bloom Jason , Cox Shelley , Anderson David , Stephenson Michael , Lefkovits Jeffrey , Taylor Andrew , Kaye David , Cullen Louise , Smith Karen , Stub Dion
Published: March 2023

Background

This study aimed to estimate the direct healthcare cost burden of acute chest pain attendances presenting to ambulance in Victoria, Australia, and to identify key cost drivers especially among low-risk patients.

Methods

State-wide population-based cohort study of consecutive adult patients attended by ambulance for acute chest pain with individual linkage to emergency and hospital admission data in Victoria, Australia (1 January 2015–30 June 2019). Direct healthcare costs, adjusted for inflation to 2020–2021 ($A), were estimated for each component of care using a casemix funding method.

Results

From 241 627 ambulance attendances for chest pain during the study period, mean chest pain episode cost was $6284, and total annual costs were estimated at $337.4 million ($68 per capita per annum). Total annual costs increased across the period ($310.5 million in 2015 vs $384.5 million in 2019), while mean episode costs remained stable. Cardiovascular conditions (25% of presentations) were the most expensive (mean $11 523, total annual $148.7 million), while a non-specific pain diagnosis (49% of presentations) was the least expensive (mean $3836, total annual $93.4 million). Patients classified as being at low risk of myocardial infarction, mortality or hospital admission (Early Chest pain Admission, Myocardial infarction, and Mortality (ECAMM) score) represented 31%–57% of the cohort, with total annual costs estimated at $60.6 million–$135.4 million, depending on the score cut-off used.

Conclusions

Total annual costs for acute chest pain presentations are increasing, and a significant proportion of the cost burden relates to low-risk patients and non-specific pain. These data highlight the need to improve the cost-efficiency of chest pain care pathways.
Left atrial phasic function: physiology, clinical assessment and prognostic value
Authors: Ferkh Aaisha , Clark Amy , Thomas Liza
Published: March 2023

Left atrial (LA) phasic function provides significant insights into the pathophysiology of cardiovascular disease. LA function is described in three phases: reservoir (atrial filling, during systole), conduit (passive emptying, during early diastole) and contractile (active emptying, during late diastole). LA phasic function can be evaluated by different imaging modalities, and a variety of techniques including volumetric analysis, deformation (strain) and Doppler methods. LA phasic function (particularly LA reservoir strain) is more sensitive and provides earlier detection of LA dysfunction than alterations in LA volume. LA function parameters have also demonstrated significant diagnostic and prognostic value, particularly in heart failure, atrial fibrillation and stroke. However, there remain barriers to implementation of phasic function parameters in clinical practice and guidelines. This review outlines the physiology of LA phasic function, methods of assessment, and its diagnostic and prognostic utility in varying pathologies.
Couple concordance in diabetes, hypertension and dyslipidaemia in urban India and Pakistan and associated socioeconomic and household characteristics and modifiable risk factors
Authors: Nielsen Jannie , Shivashankar Roopa , Cunningham Solveig A , Prabhakaran Dorairaj , Tandon Nikhil , Mohan Viswanathan , Iqbal Romaina , Narayan KM Venkat , Ali Mohammed K , Patel Shivani Anil
Published: March 2023

Background

Concordance in chronic disease status has been observed within couples. In urban India and Pakistan, little is known about couple concordance in diabetes, hypertension, and dyslipidaemia and associated socioeconomic characteristics and modifiable risk factors.

Methods

We analysed cross-sectional data from 2548 couples from the Centre for cArdio-metabolic Risk Reduction in South Asia cohort in Chennai, Delhi and Karachi. We estimated couple concordance in presence of ≥1 of diabetes, hypertension and dyslipidaemia (positive concordance: both spouses (W+H+); negative concordance: neither spouse (W−H−); discordant wife: only wife (W+H−); or discordant husband: only husband (W−H+)). We assessed associations of five socioeconomic and household characteristics, and six modifiable risk factors with couple concordance using multinomial logistic regression models with couples as the unit of analysis (reference: W−H−).

Results

Of the couples, 59.4% (95% CI 57.4% to 61.3%) were concordant in chronic conditions (W+H+: 29.2% (95% CI 27.4% to 31.0%); W−H−: 30.2% (95% CI 28.4%− to 32.0%)); and 40.6% (95% CI 38.7% to 42.6%) discordant (W+H−: 13.1% (95% CI 11.8% to 14.4%); W−H+: 27.6% (95% CI 25.9% to 29.4%)). Compared with couples with no conditions (W−H−), couples had higher relative odds of both having at least one condition if they had higher versus lower levels of: income (OR 2.03 (95% CI 1.47 to 2.80)), wealth (OR 2.66 (95% CI 1.98 to 3.58)) and education (wives’ education: OR 1.92 (95% CI 1.29 to 2.86); husbands’ education: OR 2.98 (95% CI 1.92 to 4.66)) or weight status (overweight or obesity in both spouses ORs 7.17 (95% CI 4.99 to 10.30)).

Conclusions

Positive couple concordance in major chronic conditions is high in urban India and Pakistan, especially among couples with relatively higher socioeconomic position. This suggests that prevention and management focusing on couples at high risk for concordant chronic conditions may be effective and more so in higher socioeconomic groups.
Society for Immunotherapy of Cancer (SITC) consensus definitions for resistance to combinations of immune checkpoint inhibitors with chemotherapy
Authors: Rizvi Naiyer , Ademuyiwa Foluso O , Cao Z Alexander , Chen Helen X , Ferris Robert L , Goldberg Sarah B , Hellmann Matthew D , Mehra Ranee , Rhee Ina , Park Jong Chul , Kluger Harriet , Tawbi Hussein , Sullivan Ryan J
Published: March 2023

Although immunotherapy can offer profound clinical benefit for patients with a variety of difficult-to-treat cancers, many tumors either do not respond to upfront treatment with immune checkpoint inhibitors (ICIs) or progressive/recurrent disease occurs after an interval of initial control. Improved response rates have been demonstrated with the addition of ICIs to cytotoxic therapies, leading to approvals from the US Food and Drug Administration and regulatory agencies in other countries for ICI−chemotherapy combinations in a number of solid tumor indications, including breast, head and neck, gastric, and lung cancer. Designing trials for patients with tumors that do not respond or stop responding to treatment with immunotherapy combinations, however, is challenging without uniform definitions of resistance. Previously, the Society for Immunotherapy of Cancer (SITC) published consensus definitions for resistance to single-agent anti-programmed cell death protein 1 (PD-1). To provide guidance for clinical trial design and to support analyses of emerging molecular and cellular data surrounding mechanisms of resistance to ICI-based combinations, SITC convened a follow-up workshop in 2021 to develop consensus definitions for resistance to multiagent ICI combinations. This manuscript reports the consensus clinical definitions for combinations of ICIs and chemotherapies. Definitions for resistance to ICIs in combination with targeted therapies and with other ICIs will be published in companion volumes to this paper.
Society for Immunotherapy of Cancer (SITC) consensus definitions for resistance to combinations of immune checkpoint inhibitors with targeted therapies
Authors: Atkins Michael B , Ascierto Paolo A , Feltquate David , Gulley James L , Johnson Douglas B , Khushalani Nikhil I , Sosman Jeffrey , Yap Timonthy A , Kluger Harriet , Sullivan Ryan J , Tawbi Hussein
Published: March 2023

Immunotherapy offers deep and durable disease control to some patients, but many tumors do not respond to treatment with single-agent immune checkpoint inhibitors (ICIs). One strategy to enhance responses to immunotherapy is via combinations with signal transduction inhibitors, such as antiangiogenic therapies, which not only directly target cancer cells but also could potentially favorably modulate the tumor immune microenvironment. Combination strategies with ICIs have demonstrated enhanced antitumor activity compared with tumor-targeted or antiangiogenic therapy alone in randomized trials in a variety of solid tumor settings, leading to regulatory approval from the US Food and Drug Administration and agencies in other countries for the treatment of endometrial cancer, kidney cancer, melanoma, and hepatocellular carcinoma. Despite improved survival and response rates for some patients when antiangiogenic or targeted therapies are administered with ICIs, many patients continue to progress after combination treatment and urgently need new strategies to address this manifestation of resistance to immunotherapy. Previously, the Society for Immunotherapy of Cancer (SITC) published consensus definitions for resistance to single-agent anti-PD-(L)1. To provide guidance for clinical trial design and to support analyses of emerging molecular and immune profiling data surrounding mechanisms of resistance to ICI-based combinations, SITC convened a follow-up workshop in 2021 to develop consensus definitions for resistance to multiagent ICI combinations. This manuscript reports the consensus clinical definitions for combinations of anti-PD-(L)1 ICIs and targeted therapies. Definitions for resistance to ICIs in combination with chemotherapy and with other ICIs will be published in companion volumes to this paper.
Profiling specific cell populations within the inflammatory tumor microenvironment by oscillating-gradient diffusion-weighted MRI
Authors: Hoffmann Emily , Gerwing Mirjam , Niland Stephan , Niehoff Rolf , Masthoff Max , Geyer Christiane , Wachsmuth Lydia , Wilken Enrica , Höltke Carsten , Heindel Walter L , Hoerr Verena , Schinner Regina , Berger Philipp , Vogl Thomas , Eble Johannes A , Maus Bastian , Helfen Anne , Wildgruber Moritz , Faber Cornelius
Published: March 2023

Background

The inflammatory tumor microenvironment (TME) is formed by various immune cells, being closely associated with tumorigenesis. Especially, the interaction between tumor-infiltrating T-cells and macrophages has a crucial impact on tumor progression and metastatic spread. The purpose of this study was to investigate whether oscillating-gradient diffusion-weighted MRI (OGSE-DWI) enables a cell size-based discrimination between different cell populations of the TME.

Methods

Sine-shaped OGSE-DWI was combined with the Imaging Microstructural Parameters Using Limited Spectrally Edited Diffusion (IMPULSED) approach to measure microscale diffusion distances, here relating to cell sizes. The accuracy of IMPULSED-derived cell radii was evaluated using in vitro spheroid models, consisting of either pure cancer cells, macrophages, or T-cells. Subsequently, in vivo experiments aimed to assess changes within the TME and its specific immune cell composition in syngeneic murine breast cancer models with divergent degrees of malignancy (4T1, 67NR) during tumor progression, clodronate liposome-mediated depletion of macrophages, and immune checkpoint inhibitor (ICI) treatment. Ex vivo analysis of IMPULSED-derived cell radii was conducted by immunohistochemical wheat germ agglutinin staining of cell membranes, while intratumoral immune cell composition was analyzed by CD3 and F4/80 co-staining.

Results

OGSE-DWI detected mean cell radii of 8.8±1.3 µm for 4T1, 8.2±1.4 µm for 67NR, 13.0±1.7 for macrophage, and 3.8±1.8 µm for T-cell spheroids. While T-cell infiltration during progression of 4T1 tumors was observed by decreasing mean cell radii from 9.7±1.0 to 5.0±1.5 µm, increasing amount of intratumoral macrophages during progression of 67NR tumors resulted in increasing mean cell radii from 8.9±1.2 to 12.5±1.1 µm. After macrophage depletion, mean cell radii decreased from 6.3±1.7 to 4.4±0.5 µm. T-cell infiltration after ICI treatment was captured by decreasing mean cell radii in both tumor models, with more pronounced effects in the 67NR tumor model.

Conclusions

OGSE-DWI provides a versatile tool for non-invasive profiling of the inflammatory TME by assessing the dominating cell type T-cells or macrophages.
All-trans retinoic acid improves NSD2-mediated RARα phase separation and efficacy of anti-CD38 CAR T-cell therapy in multiple myeloma
Authors: Peng Ziyi , Wang Jingya , Guo Jing , Li Xin , Wang Sheng , Xie Ying , Jiang Hongmei , Wang Yixuan , Wang Mengqi , Hu Meilin , Li Qian , Wang Yafei , Mi Jian-Qing , Liu Zhiqiang
Published: March 2023

Background

Immunotherapies targeting CD38 have demonstrated salient efficacy in relapsed/refractory multiple myeloma (MM). However, loss of CD38 antigen and outgrowth of CD38 negative plasma cells have emerged as a major obstacle in clinics. All-trans retinoic acid (ATRA) has been reported to upregulate CD38 expression, but the mechanism and adaptive genetic background remain unexplored.

Methods

The efficacy of ATRA in upregulating CD38 expression in MM cells is evaluated by flow cytometry. The interaction between NSD2 and the RARα is analyzed by immunoprecipitation, and the nuclear condensation of RARα is evaluated under laser confocal microscope. A graft model of MM is established in NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ mice, and the tumor burden is assessed by in vivo fluorescence imaging.

Results

We report that ATRA upregulates MM cells CD38 in a non-linear manner, which is t(4;14) translocation dependent, and t(4;14) translocation-induced NSD2 shows positive correlation with ATRA-induced level of, but not with basal level of CD38 expression. Mechanistically, NSD2 interacts with the ATRA receptor, RARα, and protects it from degradation. Meanwhile, NSD2 enhances the nuclear condensation of RARα and modifies the histone H3 dimethylation at lysine 36 on CD38 promoter. Knockdown of NSD2 attenuates the sensitization of MM against ATRA induced CD38 upregulation. Translationally, ATRA is prone to augment the efficacy of anti-CD38 CAR T cells in NSD2highMM cells in vitro and in vivo.

Conclusion

This study elucidates a mechanism of ATRA in regulating CD38 expression and expands the clinical potential of ATRA in improving immunotherapies against CD38 in patients with MM.Cite Now
Transition from WATCHMAN V.2.5 to WATCHMAN FLX for closure of the left atrial appendage: echocardiographic and clinical findings
Authors: Sakriss Charlotte , Roehl Peter , Schwenzky Andreas , Hoyme Matthias , Ebelt Henning
Published: March 2023

Introduction

Interventional closure of the left atrial appendage (LAAC) has been established as an alternative treatment for patients with atrial fibrillation (AF) and an elevated risk of stroke. The WATCHMAN FLX (WM FLX) as the newest WATCHMAN LAAC device differs in several technical characteristics from its precursor, the WATCHMAN V.2.5 (WM V.2.5).

Methods

The data presented here are derived from a retrospective single-centre study. All patients in which an LAAC was performed between February 2017 and March 2021 with either a WM V.2.5 or WM FLX device were included.

Results

169 patients were included in this study, of whom 95 had been treated with WM V.2.5 and 74 with WM FLX, respectively. Directly after implantation, only minor differences regarding membrane thickness and connector protrusion were noted, whereas no relevant differences were found regarding device sizing, device compression or peridevice leakage, respectively. However, at 3-month follow-up, device compression was significantly reduced in WM FLX indicating a continued device expansion which was paralleled by a reduced number of peridevice leakage in comparison to WM V.2.5. Additionally, the combined clinical endpoint of death, stroke/transistoric ischaemic attack, tamponade, device embolisation, device-related thrombosis or peridevice leakage was reduced in WM FLX.

Conclusion

LAAC using the WM FLX device results in a continued device expansion over the first 3 months based on differences in radial force in comparison to WM V.2.5. This is accompanied by a reduction in adverse clinical endpoints.