bluuebunny/crossref_metadata_2025 huggingface dataset:
Futureless vicissitudes: Gestural anti-consumption and the reflexively impotent (anti-)consumer
Authors: Hoang Quynh , Cronin James , Skandalis Alexandros
Published: January 2023

In this paper, we challenge the prevalent idea that anti-consumption functions as an ideological act of antagonism. We enlist the work of the late cultural theorist Mark Fisher to account for the reflexively impotent (anti-)consumer, a politically hollowed-out and knowingly helpless subject endemic to the futureless vicissitudes of semiocapitalist consumer culture. Drawing on netnographic data and interviews with ‘digital detoxers’, we explore how gestural – rather than transformational – anti-consumption emerges through individuals’ reflexive awareness of their political inertia, the lack of collective spirit to bring about improved conditions, and their perpetual attachment to market-based comforts and conveniences. Our analyses reveal three features that underpin the reflexively impotent (anti-)consumer’s resigned acceptance of the reigning political-ideological status quo: magical voluntarism, pragmatism and self-indulgence. In the absence of any unifying and politically-centred solidarity projects, mere gestures of resistance are undertaken towards managing personal dissatisfactions with – instead of collectively transforming – their structural conditions.
A novel data-based approach for monitoring fatigue crack propagation in welded joints under varying ambient temperature using the electromechanical admittance
Authors: Dreisbach Anna-Lena , Yokaribas Volkan , Dietrich Gerhard , Sahm Daniel , Pak Daniel , Fritzen Claus-Peter
Published: January 2023

Fatigue crack growth is one of the most common damage mechanisms of structural components and can result in a sudden and unexpected abrupt fracture which can cause catastrophic failure. Thus, monitoring of crack propagation is an important topic of structural health monitoring. For that reason, this work aims at the detection of crack propagation by the application of a high-frequency vibration-based method, using the electromechanical admittance (EMA). It enables the local monitoring of the coupled dynamic behavior of the structure and the piezoelectric transducer which changes, for example, due to damage. It is the purpose of this study to develop a method from the recorded data reflecting fatigue crack growth in weld zones. As it is known that the data are affected by temperature, a temperature compensation strategy is considered. In this study, a presentation of the coupled EMA data has been found, which allows the isolation of the crack propagation effects. Within the scope of fatigue experiments, fatigue cracks were introduced into threaded bolts of rail support points, welded onto base plates. In practice, they are embedded in a layer of mortar and, therefore, have poor accessibility. Electromechanical impedance measurements were carried out at different states of fatigue crack growth. The fatigue crack growth was validated by strain gauge measurements executed during the fatigue experiment. The proposed feature was calculated from the recorded EMA data. The technique produces promising results detecting fatigue cracks and can also be transferred to similar types of welded joints or rods where fatigue crack growth occurs.
Persisting Cancer in Black Salve Treated Skin Lesions: Results of a Large 5 Year Retrospective Analysis of Australian Histopathology Specimens
Authors: Croaker Andrew , Liu Lei , Myers Stephen P.
Published: January 2023

Background:

To date there has been minimal research on the use of black salve escharotics. Whether cancer persistence is a frequent finding in treatment areas, the types of lesion being treated by patients, whether rural patients are more likely to use black salve and whether current government prevention initiatives are succeeding are all issues needing investigation.

Methods:

This study was a large national retrospective black salve pathology case series from 2015 to 2019. Five private pathology companies with 1471 collection centers located in 5 of the 8 Australian states and Territories provided de-identified skin pathology report information where black salve treatment had been documented in the pathology request.

Results:

Over the 5-year period 409 patients had treated 475 lesions with black salve. Benign lesions were present at the treatment site in 18% of cases; persisting cancer was found in 34.2% of the remaining black salve treated areas. The majority of treatment areas were located on the head and neck. Black salve caused necrosis of normal tissue when treating benign lesions, refuting claims of cancer specificity. Likelihood of black salve use increased with rurality based on Modified Monash (MM) scores. Black salve use, despite regulatory efforts, appears to be increasing with specimen numbers more than doubling from 2015 to 2019.

Conclusions:

Patients undergoing histopathological assessment of black salve treatment areas have high rates of cancer persistence. Patients are applying black salve to benign lesions and lesions in cosmetically sensitive areas. Rural patients have higher proportional rates of black salve use. The increasing incidence of black salve pathology specimens suggests current Australian black salve public health initiatives are failing.
‘They Say it was Her Fault… This is Not True!’ Using Vignettes With Adolescent Girls to Collectively Address Norms About Sexual Violence
Authors: Pincock Kate , Verhoeven Dianne , Jones Nicola , Isimbi Roberte
Published: January 2023

This article discusses the piloting of vignette research tools within focus group discussions involving 34 adolescent girls aged 15–19 in Rwanda. The purpose of the research was to elucidate norms around sexual violence. Through a ‘collective capabilities’ lens, which focuses on ways to move beyond change at the individual level towards empowerment processes that benefit all girls, we reflect on the opportunities this methodological tool offers for expanding girls’ understanding of the norms that enable sexual violence, and the context-specific ways they can respond. After providing an overview of the vignettes exercise and the way in which the vignette on sexual violence was used with participants, we present girls’ accounts of sexual violence drawn from discussions based around the vignettes and our analysis of these findings. We find that gendered social norms around gender, sexuality, age, and responsibility for safety that apportion blame to girls who experience sexual violence play a role in preventing girls from using reporting mechanisms. Although girls have a strong sense of this being unfair, they realise they must also find ways to navigate these norms to avoid being blamed for their own victimisation. Based on this data, we suggest that the use of vignettes in the context of qualitative longitudinal research offers insights into norms about the drivers and causes of sexual violence that are otherwise challenging to elicit because of the sensitivity of the topic. We find that vignettes can be an empowering tool, both in raising ‘unspoken’ issues girls face and in creating the opportunity for girls to collectively work out pathways to accountability in a context where sexual violence is widespread but underreported. However, strategies to address sexual violence must account for barriers to reporting that include the social implications for girls of identifying perpetrators and exposing themselves to stigma and blame.
Probing pain aversion in rats with the “Heat Escape Threshold” paradigm
Authors: Hogri Roni , Baltov Bozhidar , Drdla-Schutting Ruth , Mussetto Valeria , Raphael Holzinger , Trofimova Lidia , Sandkühler Jürgen
Published: January 2023

The aversive aspect of pain constitutes a major burden faced by pain patients. This has been recognized by the pain research community, leading to the development of novel methods focusing on affective-motivational behaviour in pain model animals. The most common tests used to assess pain aversion in animals require cognitive processes, such as associative learning, complicating the interpretation of results. To overcome this issue, studies in recent years have utilized unconditioned escape as a measure of aversion. However, the vast majority of these studies quantify jumping – a common escape behaviour in mice, but not in adult rats, thus limiting its use. Here, we present the “Heat Escape Threshold” (HET) paradigm for assessing heat aversion in rats. We demonstrate that this method can robustly and reproducibly detect the localized effects of an inflammatory pain model (intraplantar carrageenan) in male and female Sprague-Dawley rats. In males, a temperature that evoked unconditioned escape following carrageenan treatment also induced real-time place avoidance (RTPA). Systemic morphine more potently alleviated carrageenan-induced heat aversion (as measured by the HET and RTPA methods), as compared to reflexive responses to heat (as measured by the Hargreaves test), supporting previous findings. Next, we examined how blocking of excitatory transmission to the lateral parabrachial nucleus (LPBN), a key node in the ascending pain system, affects pain behaviour. Using the HET and Hargreaves tests, we show that intra-LPBN application of glutamate antagonists reverses the effects of carrageenan on both affective and reflexive pain behaviour, respectively. Finally, we employed the HET paradigm in a generalized opioid-withdrawal pain model. Withdrawal from a brief systemic administration of remifentanil resulted in a long-lasting and robust increase in heat aversion, but no change in reflexive responses to heat. Taken together, these data demonstrate the utility of the HET paradigm as a novel tool in preclinical pain research.
Identifying unfamiliar voices: Examining the system variables of sample duration and parade size
Authors: Pautz Nikolas , McDougall Kirsty , Mueller-Johnson Katrin , Nolan Francis , Paver Alice , Smith Harriet M. J.
Published: January 2023

Voice identification parades can be unreliable due to the error-prone nature of earwitness responses. UK government guidelines recommend that voice parades should have nine voices, each played for 60 s. This makes parades resource-consuming to construct. In this article, we conducted two experiments to see if voice parade procedures could be simplified. In Experiment 1 ( N = 271, 135 female), we investigated if reducing the duration of the voice samples on a nine-voice parade would negatively affect identification performance using both conventional logistic and signal detection approaches. In Experiment 2 ( N = 270, 136 female), we first explored if the same sample duration conditions used in Experiment 1 would lead to different outcomes if we reduced the parade size to include only six voices. Following this, we pooled the data from both experiments to investigate the influence of target-position effects. The results show that 15-s sample durations result in statistically equivalent voice identification performance to the longer 60-s sample durations, but that the 30-s sample duration suffers in terms of overall signal sensitivity. This pattern of results was replicated using both a nine- and a six-voice parade. Performance on target-absent parades were at chance levels in both parade sizes, and response criteria were mostly liberal. In addition, unwanted position effects were present. The results provide initial evidence that the sample duration used in a voice parade may be reduced, but we argue that the guidelines recommending a parade with nine voices should be maintained to provide additional protection for a potentially innocent suspect given the low target-absent accuracy.
The attentional boost effect overcomes dual-task interference in choice-response tasks
Authors: Lee Vanessa G
Published: January 2023

Dual-task interference often arises when people respond to an incoming stimulus according to an arbitrary rule, such as choosing between the gas pedal and the brake when driving. Severe interference from response selection yields a brief “Psychological Refractory Period,” during which a concurrent task is put on hold. Here, we show that response selection in one task does not always hamper the processing of a secondary task. Responding to a target may paradoxically enhance the processing of secondary tasks, even when the target requires complex response selection. In three experiments, participants encoded pictures of common objects to memory while simultaneously monitoring a rapid serial visual presentation (RSVP) of characters or colours. Some of the RSVP stimuli were targets, requiring participants to press one of the two buttons to report their identity; others were distractors that participants ignored. Despite the increased response selection demands on target trials, pictures encoded with the RSVP targets were better remembered than those encoded with the RSVP distractors. Contrary to previous reports and predictions from dual-task interference, the attentional boost from target detection overcomes increased interference from response selection.
Visual movement impairs duration discrimination at short intervals
Authors: Torres Nathércia L , Castro São Luís , Silva Susana
Published: January 2023

The classic advantage of audition over vision in time processing has been recently challenged by studies using continuously moving visual stimuli such as bouncing balls. Bouncing balls drive beat-based synchronisation better than static visual stimuli (flashes) and as efficiently as auditory ones (beeps). It is yet unknown how bouncing balls modulate performance in duration perception. Our previous study addressing this was inconclusive: there were no differences among bouncing balls, flashes, and beeps, but this could have been due to the fact that intervals were too long to allow sensitivity to modality (visual vs auditory). In this study, we conducted a first experiment to determine whether shorter intervals elicit cross-stimulus differences. We found that short (mean 157 ms) but not medium (326 ms) intervals made duration perception worse for bouncing balls compared with flashes and beeps. In a second experiment, we investigated whether the lower efficiency of bouncing balls was due to experimental confounds, lack of realism, or movement. We ruled out the experimental confounds and found support for the hypothesis that visual movement—be it continuous or discontinuous—impairs duration perception at short interval lengths. Therefore, unlike beat-based synchronisation, duration perception does not benefit from continuous visual movement, which may even have a detrimental effect at short intervals.
Outcome following nivolumab treatment in patients with advanced non-small cell lung cancer and comorbid interstitial lung disease in a real-world setting
Authors: Assié Jean-Baptiste , Chouaïd Christos , Nunes Hilario , Reynaud Dorothée , Gaudin Anne-Françoise , Grumberg Valentine , Jolivel Ronan , Jouaneton Baptiste , Cotté François-Emery , Duchemann Boris
Published: January 2023

Background:

Up to 10% of patients with advanced non-small cell lung cancer (aNSCLC) have pre-existing interstitial lung disease (ILD). These patients are usually excluded from immunotherapy clinical trials. Consequently, knowledge on outcomes following nivolumab treatment in these patients remains limited. The primary objective of this study was to evaluate survival outcome following nivolumab treatment in ILD patients with pre-treated aNSCLC in the real-world setting.

Patients and methods:

The study included all patients with aNSCLC recorded in the French hospital database, starting nivolumab in 2015–2016. Patients were stratified by pre-existing ILD and three subgroups were studied [auto-immune or granulomatous (AI/G) ILD, other known causes ILD and idiopathic ILD]. Time to discontinuation of nivolumab treatment [time to treatment duration (TTD)] and overall survival (OS) were estimated using Kaplan–Meier survival analysis.

Results:

Of 10,452 aNSCLC patients initiating nivolumab, 148 (1.4%) had pre-existing ILD. Mean age at nivolumab initiation was 64.6 ± 9.4 years in ILD and 63.8 ± 9.6 years in non-ILD. Compared to non-ILD, patients in the ILD group were more frequently men ( p < 0.05) and had more comorbidities ( p < 0.001). There was no significant difference between ILD and non-ILD groups for median TTD (2.5 versus 2.8 months; p = 0.6) or median OS (9.6 versus 11.9 months; p = 0.1). Median OS in AI/G ILD ( n = 14), other known causes ILD ( n = 75), and idiopathic ILD ( n = 59) were 8.6, 10.7, and 9.6 months, respectively.

Conclusion:

In this large cohort of aNSCLC patients with ILD, outcomes are similar to those obtained in the non-ILD population. Immunotherapy could be beneficial for these patients.
A novel infrapatellar approach of ultrasound-guided intra-articular injection of the knee from both lateral and medial side: a case series
Authors: Lam King Hei Stanley , Wu Yung-Tsan , Reeves Kenneth Dean , Hadzic Admir , Perez Mario Fajardo , Fu Sau Nga
Published: January 2023

Knee osteoarthritis (OA) is common. Ultrasound-guided intra-articular injection (UGIAI) using the superolateral approach is currently the gold standard for treating knee OA, but it is not 100% accurate, especially in patients with no knee effusion. Herein, we present a case series of chronic knee OA treated with a novel infrapatellar approach to UGIAI. Five patients with chronic grade 2–3 knee OA, who had failed on conservative treatments and had no effusion but presented with osteochondral lesions over the femoral condyle, were treated with UGIAI with different injectates using the novel infrapatellar approach. The first patient was initially treated using the traditional superolateral approach, but the injectate was not delivered intra-articularly and became trapped in the pre-femoral fat pad. The trapped injectate was aspirated in the same session due to interference with knee extension, and the injection was repeated using the novel infrapatellar approach. All patients who received the UGIAI using the infrapatellar approach had the injectates successfully delivered intra-articularly, as confirmed with dynamic ultrasound scanning. Their Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, stiffness, and function scores significantly improved 1 and 4 weeks post-injection. UGIAI of the knee using a novel infrapatellar approach is readily learned and may improve accuracy of UGIAI, even for patients with no effusion.
Patient orientation in public hospitals: A marketing device as compromise between worlds
Authors: Gilbert Patrick , Laporte Marie-Eve
Published: January 2023

The concept of patient centricity has spread for several years in hospitals where, under the expression patient-centered care (PCC), it contributes to introducing a marketing logic in a new environment. However, beyond the intention to transform the patient as an object into a patient as a subject, this concept remains difficult to define. A review of the literature shows a diversity of approaches that are echoed in practice. This article draws on the economies of worth to examine how these conceptions collide but also reconcile. It relies on the study of an emblematic case, the orthopedic surgery department of a large Parisian public hospital (3 weeks of observation and 43 interviews). The research shows that PCC is built sequentially in a shared experience involving patients, caregivers, and management. The article defines PCC as a marketing device resulting from compromises between different conventions and provides evolution scenarios.
Getting a Seat at the Table: Changes in Military Participation in Government and Coups
Authors: White Peter B
Published: January 2023

Why do coups happen and how can state leaders affect their likelihood? Existing research focuses on structural factors as well as “coup-proofing” as drivers of coup risk. I argue that the literature misses an important alternative avenue by which leaders affect the likelihood that their militaries remove them from office: adding or removing military officers from the government. When leaders bring military officers into the government, they signal to the military that there is a peaceful path to sharing power and provide an alternative to coups. In contrast, removing military officers from government dramatically increases the risk of a coup attempt as the military retaliates against the leader’s power grab. I test this theory using cross-national data that captures changes in military representation in national cabinets and state councils from 1969 to 2008 and find mixed support. In line with the theory, there is strong evidence that large reductions in the military’s government positions lead to coup attempts, and more modest evidence that large increases reduce coup attempts. However, contrary to expectations, the results also suggest that small increases in military government positions increase the risk of a coup.
Impact of Competition in Credit Rating Industry: Evidence From India
Authors: Sharma Chandan , Singh Archana , Yadav Rajan
Published: January 2023

Credit rating agencies (CRAs) play an essential role in efficiently allocating capital in the financial system. However, several researchers have highlighted shortcomings of CRAs, leading to drastic consequences such as the 2008 financial crisis. The paper focuses on the competition among CRAs as one of the critical drivers of issues plaguing the credit rating industry. The paper uses quantitative and regression techniques to check the impact of competition on a firm’s credit rating. The paper utilizes firm-level financial and credit rating data from India. The paper uses dual ratings to check whether competition leads to rating inflation and shopping practices in the credit rating industry. The paper finds that CRA inflates a firm’s credit rating due to competition from other CRAs. Rating shopping is also evident in the credit rating industry, driven by competition between CRAs to gain new clients. The paper’s findings also indicate that increased competition for large-size firms business leads to CRAs showing leniency when rating such firms. The results raise the need for regulators to actively monitor and control the competition among CRAs to ensure the accuracy of credit ratings.
The Impact of the COVID-19 Crisis on Air Travel Demand: Some Evidence From China
Authors: Wu Xi , Blake Adam
Published: January 2023

This paper applies a three-step framework to quantify COVID-19’s impacts on China’s domestic and international air travel demand and to evaluate how the impacts evolve from January 2020 to January 2022. Time series techniques and combination forecasting are tested to identify the best-performing model to generate baseline forecasts, with which actual demands are compared to assess the impact of COVID-19. The results demonstrate that during the period under study, China’s domestic aviation sector experienced two V-shape recoveries, while its international counterpart was devastated and showed no sign of revival. It suggests that to mitigate the impact of COVID-19, containing virus spread and removing mobility controls are essential; and when travel restrictions are lifted or loosened, governments play important roles in accelerating the rate of demand recovery.
Soft Power in emerging economies: A partial least squares – structural equation modeling exploratory analysis of the effects on outward foreign direct investment
Authors: Buitrago R. Ricardo E. , Rajasekar James , Alcaraz Jorge
Published: January 2023

This article discusses the linkage between Soft Power institutional conditions and their effects on inward foreign direct investment (IFDI) as a mediator of outward foreign direct investment (OFDI). We measured Soft Power through the use of selected indicators between 2016 and 2019. To evaluate the proposed Soft Power constructs and their relationship with IFDI – OFDI, we applied partial least squares – structural equation modeling (PLS-SEM) analysis. The model outcomes suggest that Government, Business, Culture, and Diplomacy conditions have a significant and positive effect on IFDI and OFDI. The findings are context-moderated due to the heterogeneity of the emerging economies evaluated.
Music and discourse: A systemic-functional approach for music analysis in multimodal contexts
Authors: Forte Diego L
Published: January 2023

Meaning in music constitutes an issue that have risen (and still rises) a strong debate. Although it has been approached from different perspectives there seems to be no consensus for its theorization. From a Social Semiotic perspective, music can be analysed as a part of a bigger construction, sharing the task of making meaning with other modes (verbal, visual, etc.). This paper aims to make a contribution to multimodal studies proposing a way to include music analysis in Multimodal Critical Discourse Analysis. We adopt as framework Halliday’s theory (1978 ; 1994) , although we start from Kress and van Leeuwen (2020) adaptations and include McKerrell (2015) and van Leeuwen (1999). Our working hypothesis is that, in multimodal contexts, music contributes with the construction of meaning, particularly ideational meaning, establishing a relation with other modes.
Addressing the needs of marginalised young people through school-based catch-up interventions during COVID-19: A case study from Ireland
Authors: Keane Elaine , Flynn Niamh , Kealy Carmen
Published: January 2023

In 2020, schools worldwide closed due to the COVID-19 pandemic. Almost one million young people and children were impacted in Ireland, with those from ‘marginalised’ backgrounds being especially vulnerable due to pre-existing inequalities. The Crisis Coping for Marginalised Young People: Living and Learning through COVID- 19 project aimed to explore youth pandemic life and learning experiences and to support the needs of, particularly marginalised, young people, culminating in the implementation of supports for students in schools. Here, we present a praxeological account of the benefits and challenges associated with our novel methodology which involved working ‘through’ 14 final-year student teachers’ practitioner research projects in their designated disadvantaged or socio-demographically diverse placement schools (11) across six counties in the Republic of Ireland, involving 269 students. Supervised closely by the lead researchers, the teacher-researchers conducted empirical research in their schools (involving questionnaires with students and interviews with Principals) to inform the design of academic, social and mixed school-based interventions which were subsequently implemented and evaluated. The empirical findings pointed to young people’s concerns about social isolation, the stability of friendships and having fallen behind academically, and Principals’ concerns about supporting those from marginalised backgrounds and about creating a safe and happy environment upon return to in-person school. In this paper, we highlight our significantly improved understanding of the COVID-related experiences of young people from marginalised backgrounds but point to the uncertain effectiveness of the interventions for improving their educational readjustment. Further, we critically interrogate the challenges encountered which constrained the lead researchers’ and teacher-researchers’ actions.
The pragmatic structure of indeterminacy: Mapping possibilities as context for action
Authors: Baumeister Roy F , Alquist Jessica L
Published: January 2023

Social psychology studies how situations cause behavior. Situations are partly defined by a matrix of possibilities (including probabilities and contingencies), and so human responses are caused not merely by realities but also by possibilities—even including some possibilities that never materialize. The human mind has complex abilities to recognize, imagine, and deal with possibilities. Two important dimensions of possibility, here labeled horizontal and vertical, differ as to how controllable the outcome is for any particular agent and where the value basis originates. Success/failure is an example of the vertical dimension and normally is only partly controllable, whereas open choice such as ordering off a menu is an example of the horizontal dimension. Possibilities and agency develop complex relationships to time: The future is defined by alternative possibilities whereas the past cannot be changed, though it can be re-imagined counterfactually and also reinterpreted. Last, we highlight the problem of how possibilities and probabilities combine. Statistical analysis of variance strategies offer three models of combination: independent and additive (like main effects), damping versus intensifying each other (as in spreading interactions), or reversing each other’s effects (as in crossover interactions).
Delayed normalisation of ADAMTS13 activity in acute Thrombotic Thrombocytopenic Purpura in the caplacizumab era
Authors: Prasannan Nithya , Thomas Mari , Stubbs Matthew James , Westwood John-Paul , de Groot Rens , Singh Deepak , Scully Marie
Published: January 2023

The benefits of caplacizumab in acute immune mediated TTP (iTTP) are well established. We identified a delay in normalisation of ADAMTS13 activity (>30%) in a subgroup of caplacizumab treated patients which was not evident in the pre-caplacizumab era. Caplacizumab treated patients (n=64) achieved ADAMTS13 activity >30% at median 31 days post PEX, compared to 11.5 days in the non-caplacizumab group (n=50, p=0.0004). 18/64 (28%) caplacizumab treated patients had an ADAMTS13 activity <10% at the time of stopping caplacizumab with a longer time to ADAMTS13 activity >30% (median 139 days after completing PEX). 18/64 (28%) of patients receiving extended caplacizumab (31-58 days) failed to achieve ADAMTS13 activity >30% at time of stopping caplacizumab compared to 4/47 (8.5%) of historical controls at similar timepoint (30+28 days, p<0.0001). Failure to achieve ADAMTS13 activity >30% within 30+28 days was 6 times more likely in caplacizumab treated patients (OR 6.3, p=0.0006). ADAMTS13 antigen level <30% at caplacizumab cessation was associated with increased iTTP recurrence (4/10 vs 0/9 in patients with ADAMTS13 antigen ≥30%). Admission anti-ADAMTS13 IgG antibody level did not predict recurrence. Anti-ADAMTS13 IgG antibody levels, immunosuppression and ethnicity did not account for differences in ADAMTS13 activity response. ADAMTS13 antigen levels ≥30% may be useful to guide stopping caplacizumab therapy after extended use in patients with ADAMTS13 activity <10%, but patients require close monitoring. The reason for delayed ADAMTS13 normalisation is unclear and requires further investigation.
Newly discovered roles of triosephosphate isomerase including functions within the nucleus
Authors: Myers Tracey D. , Palladino Michael J.
Published: January 2023

Triosephosphate isomerase (TPI) is best known as a glycolytic enzyme that interconverts the 3-carbon sugars dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P). TPI is an essential enzyme that is required for the catabolism of DHAP and a net yield of ATP from anaerobic glucose metabolism. Loss of TPI function results in the recessive disease TPI Deficiency (TPI Df). Recently, numerous lines of evidence suggest the TPI protein has other functions beyond glycolysis, a phenomenon known as moonlighting or gene sharing. Here we review the numerous functions ascribed to TPI, including recent findings of a nuclear role of TPI implicated in cancer pathogenesis and chemotherapy resistance.
PP-DDP: a privacy-preserving outsourcing framework for solving the double digest problem
Authors: Suo Jingwen , Gu Lize , Yan Xingyu , Yang Sijia , Hu Xiaoya , Wang Licheng
Published: January 2023

Background

As one of the fundamental problems in bioinformatics, the double digest problem (DDP) focuses on reordering genetic fragments in a proper sequence. Although many algorithms for dealing with the DDP problem were proposed during the past decades, it is believed that solving DDP is still very time-consuming work due to the strongly NP-completeness of DDP. However, none of these algorithms consider the privacy issue of the DDP data that contains critical business interests and is collected with days or even months of gel-electrophoresis experiments. Thus, the DDP data owners are reluctant to deploy the task of solving DDP over cloud.

Results

Our main motivation in this paper is to design a secure outsourcing computation framework for solving the DDP problem. We at first propose a privacy-preserving outsourcing framework for handling the DDP problem by using a cloud server; Then, to enable the cloud server to solve the DDP instances over ciphertexts, an order-preserving homomorphic index scheme (OPHI) is tailored from an order-preserving encryption scheme published at CCS 2012; And finally, our previous work on solving DDP problem, a quantum inspired genetic algorithm (QIGA), is merged into our outsourcing framework, with the supporting of the proposed OPHI scheme. Moreover, after the execution of QIGA at the cloud server side, the optimal solution, i.e. two mapping sequences, would be transferredpubliclyto the data owner. Security analysis shows that from these sequences, none can learn any information about the original DDP data. Performance analysis shows that the communication cost and the computational workload for both the client side and the server side are reasonable. In particular, our experiments show that PP-DDP can find optional solutions with a high success rate towards typical test DDP instances and random DDP instances, and PP-DDP takes less running time than DDmap, SK05 and GM12, while keeping the privacy of the original DDP data.

Conclusion

The proposed outsourcing framework, PP-DDP, is secure and effective for solving the DDP problem.
Systematic and benchmarking studies of pipelines for mammal WGBS data in the novel NGS platform
Authors: Lin Qun-ting , Yang Wei , Zhang Xin , Li Qi-gang , Liu Yong-feng , Yan Qin , Sun Lei
Published: January 2023

Background

Whole genome bisulfite sequencing (WGBS), possesses the aptitude to dissect methylation status at the nucleotide-level resolution of 5-methylcytosine (5-mC) on a genome-wide scale. It is a powerful technique for epigenome in various cell types, and tissues. As a recently established next-generation sequencing (NGS) platform, GenoLab M is a promising alternative platform. However, its comprehensive evaluation for WGBS has not been reported. We sequenced two bisulfite-converted mammal DNA in this research using our GenoLab M and NovaSeq 6000, respectively. Then, we systematically compared those data via four widely used WGBS tools (BSMAP, Bismark, BatMeth2, BS-Seeker2) and a new bisulfite-seq tool (BSBolt). We interrogated their computational time, genome depth and coverage, and evaluated their percentage of methylated Cs.

Result

Here, benchmarking a combination of pre- and post-processing methods, we found that trimming improved the performance of mapping efficiency in eight datasets. The data from two platforms uncovered ~ 80% of CpG sites genome-wide in the human cell line. Those data sequenced by GenoLab M achieved a far lower proportion of duplicates (~ 5.5%). Among pipelines, BSMAP provided an intriguing representation of 5-mC distribution at CpG sites with 5-mC levels > ~ 78% in datasets from human cell lines, especially in the GenoLab M. BSMAP performed more advantages in running time, uniquely mapped reads percentages, genomic coverage, and quantitative accuracy. Finally, compared with the previous methylation pattern of human cell line and mouse tissue, we confirmed that the data from GenoLab M performed similar consistency and accuracy in methylation levels of CpG sites with that from NovaSeq 6000.

Conclusion

Together we confirmed that GenoLab M was a qualified NGS platform for WGBS with high performance. Our results showed that BSMAP was the suitable pipeline that allowed for WGBS studies on the GenoLab M platform.
Ratio of carbon dioxide veno-arterial difference to oxygen arterial-venous difference is not associated with lactate decrease after fluid bolus in critically ill patients with hyperlactatemia: results from a prospective observational study
Authors: Kaefer Keitiane , Pierrakos Charalampos , Nguyen Thomas , Velissaris Dimitrios , Attou Rachid , Devriendt Jacques , Scolletta Sabino , Taccone Fabio Silvio
Published: January 2023

Background

High ratio of the carbon dioxide veno-arterial difference to the oxygen arterial-venous difference (PvaCO2/CavO2) is associated with fluid bolus (FB) induced increase in oxygen consumption (VO2). This study investigated whether PvaCO2/CavO2 was associated with decreases in blood-lactate levels FB in critically ill patients with hyperlactatemia.

Methods

This prospective observational study examined adult patients in the intensive care unit (ICU) with lactate levels > 1.5 mmol/L who received FBs. Blood-lactate levels were measured before and after FB under unchanged metabolic, respiratory, and hemodynamic conditions. The primary outcome was blood-lactate levels after FB. Significant decreases in blood-lactate levels were considered as blood-lactate levels < 1.5 mmol/L or a decrease of more than 10% compared to baseline.

Results

The study enrolled 40 critically ill patients, and their median concentration of blood lactate was 2.6 [IQR:1.9 − 3.8] mmol/L. There were 27 (68%) patients with PvaCO2/CavO2 ≥ 1.4 mmHg/ml, and 10 of them had an increase in oxygen consumption (dVO2) ≥ 15% after FB, while 13 (32%) patients had PvaCO2/CavO2 < 1.4 mmHg/ml before FB, and none of them had dVO2 ≥ 15% after FB. FB increased the cardiac index in patients with high and low preinfusion PvaCO2/CavO2 (13.4% [IQR: 8.3 − 20.2] vs. 8.8% [IQR: 2.9 − 17.4], p = 0.34). Baseline PvaCO2/CavO2 was not found to be associated with a decrease in blood lactate after FB (OR: 0.88 [95% CI: 0.39 − 1.98], p = 0.76). A positive correlation was observed between changes in blood lactate and baseline PvaCO2/CavO2 (r = 0.35, p = 0.02).

Conclusions

In critically ill patients with hyperlactatemia, PvaCO2/CavO2 before FB cannot be used to predict decreases in blood-lactate levels after FB. Increased PvaCO2/CavO2 is associated with less decrease in blood-lactate levels.
Multivariate decomposition of gender differentials in successful aging among older adults in India
Authors: Srivastava Shobhit , Muhammad T. , Paul Ronak , Khan Kacho Amir
Published: January 2023

Background

Rowe and Kahn define successful aging as a high physical, psychological, and social functioning in old age without major diseases. It is considered a viable solution to the burdens placed on healthcare systems and financial and social security in societies with aging population. The present study aimed to determine the prevalence of successful aging and explore the factors contributing to gender differentials in successful aging among older adults in India.

Methods

This study utilized data from the nationally representative Longitudinal Ageing Study in India, conducted in 2017–18. The study is based on a sample of 15,098 older men and 16,366 older women aged 60 years and above. The outcome variable was a dichotomous measure of successful aging with six components including absence of chronic diseases, free from disability, high cognitive ability, free from depressive symptoms, active social engagement in life and free from obesity. Older adults satisfying all these conditions were considered aging successfully. Descriptive and bivariate analyses were carried out. Proportion test was used to evaluate the gender differentials and reflect the statistical significance in the associated factors. Multivariate decomposition analysis was conducted to identify covariates’ contribution in explaining the gender differences in successful aging.

Results

There was a significant gender difference in successful aging among older adults in India (Difference: 8.7%; p-value < 0.001] with 34.3% older men and 25.6% older women experiencing successful aging. A proportion of 88% of gender difference in successful aging was explained by the differences in the distribution of characteristics (Coef: 0.082; p-value < 0.05). Considerable gender gap in successful aging would be reduced if women had similar levels of work status (28% reduction) to their male counterparts. Bringing the level of frequent physical activity in women to the same levels observed in men would reduce the gender gap by 9%.

Conclusions

The findings suggest that women had a lower score in successful aging, which is attributed to several socioeconomic and behavioural factors including not working status and physical inactivity. More studies must be done to explore the reasons for such differences and what particular factors in low-income countries create differences among older men and women in achieving successful aging.
Protocol for a confirmatory trial of the effectiveness and safety of palliative arterial embolization for painful bone metastases
Authors: Zenda Sadamoto , Arai Yasunori , Sugawara Shunsuke , Inaba Yoshitaka , Hashimoto Kazuki , Yamamoto Kouji , Saigusa Yusuke , Kawaguchi Takashi , Shimada Sanae , Yokoyama Marie , Miyaji Tempei , Okano Tomoka , Nakamura Naoki , Kobayashi Eisuke , Takagi Tatsuya , Matsumoto Yoshihisa , Uchitomi Yosuke , Sone Miyuki ,   for the J-SUPPORT 1903, PALEM Trial
Published: January 2023

Background

Transcatheter arterial embolization (TAE) has long been used for hemostasis of traumatic or postoperative hemorrhage and embolization of tumors. Previous retrospective studies of TAE for painful bone metastases showed 60%–80% pain reduction with a median time to response of 1–2 days. Compared with radiotherapy and bisphosphonates, time to response appeared earlier than that of radiotherapy or bone-modifying agents. However, few prospective studies have examined TAE for this indication. Here, we describe the protocol for a confirmatory study designed to clarify the efficacy and safety profile of TAE.

Methods

This study will be a multicenter, single-arm confirmatory study (phase 2–3 design). Patients with painful bone metastases from any primary tumor are eligible for enrollment. TAE will be the main intervention. Following puncture of the femoral artery under local anesthesia and insertion of an angiographic sheath, angiography will confirm that the injected region includes tumor vasculature. Catheter position will be adjusted so that the embolization range does not include non-target tissues. Spherical embolic material will then be slowly injected into the artery to embolize it. The primary endpoint (efficacy) is the proportion of subjects with pain relief at 72 h after TAE and the secondary endpoint (safety) is the incidence of all NCI Common Terminology Criteria for Adverse Events version 5.0 Grade 4 adverse events and Grade ≥ 3 necrosis of the central nervous system.

Discussion

If the primary and secondary endpoints are met, TAE can be a treatment choice for painful bone metastases. Trial registry number is UMIN-CTR ID: UMIN000040794.

Trial registration

The study is ongoing, and patients are currently being enrolled. Enrollment started in March 2021. A total of 36 patients have participated as of Aug 2022.

Protocol Version: Ver1.4, 13/07/2022.
Using CT radiomic features based on machine learning models to subtype adrenal adenoma
Authors: Qi Shouliang , Zuo Yifan , Chang Runsheng , Huang Kun , Liu Jing , Zhang Zhe
Published: January 2023

Background

Functioning and non-functioning adrenocortical adenoma are two subtypes of benign adrenal adenoma, and their differential diagnosis is crucial. Current diagnostic procedures use an invasive method, adrenal venous sampling, for endocrinologic assessment.

Methods

This study proposes establishing an accurate differential model for subtyping adrenal adenoma using computed tomography (CT) radiomic features and machine learning (ML) methods. Dataset 1 (289 patients with adrenal adenoma) was collected to develop the models, and Dataset 2 (54 patients) was utilized for external validation. Cuboids containing the lesion were cropped from the non-contrast, arterial, and venous phase CT images, and 1,967 features were extracted from each cuboid. Ten discriminative features were selected from each phase or the combined phases. Random forest, support vector machine, logistic regression (LR), Gradient Boosting Machine, and eXtreme Gradient Boosting were used to establish prediction models.

Results

The highest accuracies were 72.7%, 72.7%, and 76.1% in the arterial, venous, and non-contrast phases, respectively, when using radiomic features alone with the ML classifier of LR. When features from the three CT phases were combined, the accuracy of LR reached 83.0%. After adding clinical information, the area under the receiver operating characteristic curve increased for all the machine learning methods except for LR. In Dataset 2, the accuracy of LR was the highest, reaching 77.8%.

Conclusion

The radiomic features of the lesion in three-phase CT images can potentially suggest the functioning or non-functioning nature of adrenal adenoma. The resulting radiomic models can be a non-invasive, low-cost, and rapid method of minimizing unnecessary testing in asymptomatic patients with incidentally discovered adrenal adenoma.
Final analysis of the phase 3 randomized clinical trial comparing HD201 vs. referent trastuzumab in patients with ERBB2-positive breast cancer treated in the neoadjuvant setting
Authors: Pivot Xavier , Manikhas Alexey Georgievitch , Shamrai Volodymyr , Dzagnidze Giorgi , Soo Hoo Hwoei Fen , Kaewkangsadan Viriya , Petrelli Fausto , Villanueva Cristian , Kim Jamie , Pradhan Sumita , Jaison Litha , Feyaerts Peggy , Kaufman Leonard , Derde Marie-Paule , Deforce Filip , Cox David G.
Published: January 2023

Background

The TROIKA trial established that HD201 and trastuzumab were equivalent in terms of primary endpoints (total pathological complete response) following neoadjuvant treatment. The objective of the present analysis was to compare survival outcomes and final safety.

Methods

In the TROIKA trial, patients with ERBB2-positive early breast cancer were randomized and treated with either HD201 or the referent trastuzumab. Eligible patients received 8 cycles of either HD201 or referent trastuzumab (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) every 3 weeks in combination with 8 cycles of chemotherapy (4 cycles of docetaxel, 75 mg/m2, followed by 4 cycles of epirubicin, 75 mg/m2, and cyclophosphamide, 500 mg/m2) in the neoadjuvant setting. The patients then underwent surgery followed by 10 cycles of adjuvant HD201 or referent trastuzumab according to their initial randomization to complete one year of trastuzumab-directed therapy. Event-free and overall survival rates were calculated using Kaplan–Meier analysis. The hazard ratio for event-free survival was estimated by Cox proportional hazards regression.

Results

The final analysis was performed after all patients completed the study at a median follow-up of 37.7 months (Q1-Q3, 37.3–38.1 months). A total of 502 randomized patients received either HD201 or the referent trastuzumab, and 474 (94.2%) were eligible for inclusion in the per-protocol set. In this population, the 3-year event-free survival rates were 85.6% (95% CI: 80.28–89.52) and 84.9% (95% CI: 79.54–88.88) in the HD201 and referent trastuzumab groups, respectively (log rank p = 0.938) (HR 1.02, 95% CI: 0.63–1.63; p = 0.945). The 3-year overall survival rates were comparable between the HD201 (95.6%; 95% CI: 91.90–97.59) and referent trastuzumab treatment groups (96.0%, 95% CI: 92.45–97.90) (log rank p = 0.606). During the posttreatment follow-up period, adverse events were reported for 64 (27.4%) and 72 (29.8%) patients in the HD201 and the reference trastuzumab groups, respectively. Serious adverse events were rare and none of which were related to the study treatment.

Conclusions

This final analysis of the TROIKA trial further confirms the comparable efficacy and safety of HD201 and trastuzumab.

Trial registration

ClinicalTrials.gov identifier: NCT03013504.