bluuebunny/crossref_metadata_2025 huggingface dataset:
On the 𝑝-negative type gap of finite metric spaces and its relation to the Gramian matrix
Authors: Robertson Gavin
Published: July 2024

The

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Political Resistance in Turkey: How Resistance Is Experienced and How It Has Changed Over the Last Decade
Authors: Acar Yasemin Gülsüm , Uluğ Özden Melis , Solak Nevin , Şen Ercan
Published: July 2024

This chapter focuses on resistance practices in Turkey and how these practices have adapted and changed in response to repressive tactics from the Turkish government over the last ten years. Turkey is now classified as a competitive authoritarian regime, and has become less and less democratic as its authoritarianism has risen. In the past ten years, collective action in the context of this authoritarianism has also changed forms. We examine three cases from the last decade to describe this change: (1) the Gezi Park protests, (2) online campaigns around elections, and (3) the Academics for Peace petition and its aftermath. We discuss how repression leads to more varied, creative forms of resistance and how these may continue despite further punitive measures.
The Kurdish Struggle: Multiple Ways of Resisting in a Historically Oppressive Context
Authors: Ünal Helin , Coşkan Canan
Published: July 2024

This chapter discusses findings from a qualitative study exploring how Kurds (from Turkey and Northern Kurdistan, living in Germany), a historically oppressed but resisting group, respond to oppression in the context of asymmetrical group relations that assume they are powerless. We examine various resistance strategies against historical and ongoing oppression that these members of a diasporic Kurdish community expressed. Our analysis shows that Kurdish resistance strategies go beyond typical collective actions and are shaped by collective memories, critical consciousness, and perceived power. Our chapter shows that in long-term resistance against historical and systemic oppression, which also involves various types of repression, overt resistance actions may vary considerably and not always be limited to just one tactic. Instead, people combine multiple resistance strategies simultaneously in their struggle to respond more effectively to the circumstances of oppression. Moreover, people support different resistance strategies depending on their circumstances and the ingroup’s perceived needs.
The Dynamics of Leadership and Resistance in Repressive Regimes
Authors: Jurstakova Klara , Ntontis Evangelos , Nigbur Dennis
Published: July 2024

Leadership—particularly identity leadership—remains a relatively under-researched area in the social psychological literature on resistance in violent or repressive contexts. This chapter examines how leaders mobilized overt resistance in the Czechoslovak Socialist Republic and the Polish People’s Republic. Both regimes were led by a single-party monopoly, characterized by severe repression of political and non-political activities that were perceived as threatening to the status quo, or as promoting identities inconsistent with the dominant ideology. We present an analysis of interviews and archival data, focusing on how resistance leaders overcame obstacles placed by those in power and organized resistance in the form of collective action. Leaders engaged in adaptive changes in their strategies, built a shared social identity to mobilize resistance, and gave agency to followers—allowing them to unite and sustain the movement. This chapter enhances our understanding of the psychology of leadership in mobilizing collective action under repression.
Exploring functional conservation in silico: a new machine learning approach to RNA-editing
Authors: Zawisza-Álvarez Michał , Peñuela-Melero Jesús , Vegas Esteban , Reverter Ferran , Garcia-Fernàndez Jordi , Herrera-Úbeda Carlos
Published: July 2024

Around 50 years ago, molecular biology opened the path to understand changes in forms, adaptations, complexity, or the basis of human diseases through myriads of reports on gene birth, gene duplication, gene expression regulation, and splicing regulation, among other relevant mechanisms behind gene function. Here, with the advent of big data and artificial intelligence (AI), we focus on an elusive and intriguing mechanism of gene function regulation, RNA editing, in which a single nucleotide from an RNA molecule is changed, with a remarkable impact in the increase of the complexity of the transcriptome and proteome. We present a new generation approach to assess the functional conservation of the RNA-editing targeting mechanism using two AI learning algorithms, random forest (RF) and bidirectional long short-term memory (biLSTM) neural networks with an attention layer. These algorithms, combined with RNA-editing data coming from databases and variant calling from same-individual RNA and DNA-seq experiments from different species, allowed us to predict RNA-editing events using both primary sequence and secondary structure. Then, we devised a method for assessing conservation or divergence in the molecular mechanisms of editing completely in silico: the cross-testing analysis. This novel method not only helps to understand the conservation of the editing mechanism through evolution but could set the basis for achieving a better understanding of the adenosine-targeting mechanism in other fields.
SVDF: enhancing structural variation detect from long-read sequencing via automatic filtering strategies
Authors: Hu Heng , Gao Runtian , Gao Wentao , Gao Bo , Jiang Zhongjun , Zhou Murong , Wang Guohua , Jiang Tao
Published: July 2024

Structural variation (SV) is an important form of genomic variation that influences gene function and expression by altering the structure of the genome. Although long-read data have been proven to better characterize SVs, SVs detected from noisy long-read data still include a considerable portion of false-positive calls. To accurately detect SVs in long-read data, we present SVDF, a method that employs a learning-based noise filtering strategy and an SV signature-adaptive clustering algorithm, for effectively reducing the likelihood of false-positive events. Benchmarking results from multiple orthogonal experiments demonstrate that, across different sequencing platforms and depths, SVDF achieves higher calling accuracy for each sample compared to several existing general SV calling tools. We believe that, with its meticulous and sensitive SV detection capability, SVDF can bring new opportunities and advancements to cutting-edge genomic research.
Courtship dance similarity, but not complexity, may explain patterns of hybridization in manakins (Aves: Pipridae)
Authors: Ottenburghs Jente
Published: July 2024

Differences in behaviour can play an important role in the emergence of species and the maintenance of species boundaries. In birds, behavioural isolation mechanisms range from simple vocalizations to elaborate courtship displays. The breakdown of these isolation mechanisms could result in the production of viable hybrid offspring. In general, we might expect a negative relationship between the complexity of a behavioural isolation mechanism and the incidence of hybridization. I tested this prediction in manakins, a Neotropical bird family that shows a large variety of courtship displays. I compiled a database of reliable hybrid records and quantified the complexity of species-specific courtship displays. Binary logistic regressions indicated that courtship similarity was a better predictor of hybridization probability than courtship complexity. However, this pattern was strongly influenced by phylogenetic relatedness, in that closely related species exhibited similar courtship displays that were already being performed by their common ancestor. The main limitation of this study concerns the incomplete dataset. I could assess the courtship complexity for only 22 manakin species; consequently, not all hybrid combinations could be included in the analyses. Nonetheless, these findings provide important insights into the role of courtship displays in explaining patterns of hybridization.
Different patterns of structural network impairments in two amyotrophic lateral sclerosis subtypes driven by 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance hybrid imaging
Authors: Feng Feng , Feng Guozheng , Liu Jiajin , Hao Weijun , Huang Weijie , Bi Xiao , Li Mao , Wang Hongfen , Yang Fei , He Zhengqing , Bai Jiongming , Wang Haoran , Ma Guolin , Xu Baixuan , Shu Ni , Huang Xusheng
Published: July 2024

The structural network damages in amyotrophic lateral sclerosis patients are evident but contradictory due to the high heterogeneity of the disease. We hypothesized that patterns of structural network impairments would be different in amyotrophic lateral sclerosis subtypes by a data-driven method using 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance hybrid imaging. The data of positron emission tomography, structural MRI and diffusion tensor imaging in fifty patients with amyotrophic lateral sclerosis and 23 healthy controls were collected by a 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance hybrid. Two amyotrophic lateral sclerosis subtypes were identified as the optimal cluster based on grey matter volume and standardized uptake value ratio. Network metrics at the global, local and connection levels were compared to explore the impaired patterns of structural networks in the identified subtypes. Compared with healthy controls, the two amyotrophic lateral sclerosis subtypes displayed a pattern of a locally impaired structural network centralized in the sensorimotor network and a pattern of an extensively impaired structural network in the whole brain. When comparing the two amyotrophic lateral sclerosis subgroups by a support vector machine classifier based on the decreases in nodal efficiency of structural network, the individualized network scores were obtained in every amyotrophic lateral sclerosis patient and demonstrated a positive correlation with disease severity. We clustered two amyotrophic lateral sclerosis subtypes by a data-driven method, which encompassed different patterns of structural network impairments. Our results imply that amyotrophic lateral sclerosis may possess the intrinsic damaged pattern of white matter network and thus provide a latent direction for stratification in clinical research.
Gender Gaps in Housework Activities in Europe before and after COVID-19
Authors: Angelici Marta , Savio Giulia
Published: July 2024

We use data from the European working condition survey to describe the frequency of housework activities by men and women before and after the COVID-19 pandemic in European countries. We find that, although women continue to spend more time than men in housework activities, men increase housework activities after the pandemic and the gender gaps narrow. The result is driven by countries initially characterized by larger gender gaps in housework activities.
Anomalous drainage of inferior vena cava into left atrium associated with ostium secundum atrial septal defect: a case report
Authors: Asotra Sanjeev , Kumar Ritesh , Dhaulta Praveen , Verma Mansi
Published: July 2024

Background

Anomalous drainage of inferior vena cava (IVC) into left atrium (LA) is a rare aetiology of cyanosis in adults. This condition may be associated with atrial septal defects, anomalous pulmonary venous drainage, and pulmonary arteriovenous fistulas. This case report presents an instance of anomalous drainage of IVC into LA, associated with ostium secundum atrial septal defect (ASD). It contributes to the existing literature by highlighting the diagnostic challenges associated with this anomaly, particularly during surgical intervention.

Case summary

A 38-year-old male presented with a six-year history of exertional dyspnoea and episodic palpitation. Transthoracic echocardiography revealed a large secundum (ASD), the IVC draining into LA, a left superior vena cava, and mild mitral regurgitation. These findings were further confirmed by right and left heart catheterization and CT angiogram. The patient was referred to CTVS department for surgical correction. The post-operative course was uneventful. At a 1.4-year follow-up, the patient reported significant improvement in symptoms.

Discussion

We present a case of anomalous drainage of IVC into LA, associated with ostium secundum ASD. An ASD co-occurs with this condition in ∼70% of the reported cases. This anomaly differs from a low or inferior vena caval secundum ASD, where a prominent Eustachian valve can cause blood shunting from the IVC to LA. If the surgeon is not vigilant, this can be mistaken for the inferior ASD rim, potentially leading to iatrogenic diversion of IVC blood to LA upon ASD closure, resulting in cyanosis. This case underscores the diagnostic and surgical challenges associated with this condition.
Recurrent left main stem stenosis in a young female with Behçet’s aortitis: a case report
Authors: Dardas Sotirios , Antoun Ibrahim , Sher Falik , Munir Navid , Kontoprias Kosmas
Published: July 2024

Background

Behçet’s disease (BD) is a rare and complex vasculitis disorder renowned for its diverse clinical presentations. Cardiovascular involvement is reported to be present in 7–46% of the patients, with coronary arteries being involved in only 0.5%. The management of cardiovascular complications can be challenging due to the rarity of such cases and the absence of standardized guidelines regarding diagnosis and treatment.

Case summary

We report the case of a 27-year-old patient with BD with known aortitis and pulmonary arteritis, who presented with recurrent acute coronary syndromes related to critical left main coronary artery stenosis. She was initially managed with percutaneous coronary interventions twice. Following recurrent stent failure, she eventually underwent urgent coronary artery bypass surgery, together with aortic valve replacement and aortic root repair. She made an uneventful recovery and remains well 6 months following her operation.

Discussion

This case illustrates the significant challenges that can be encountered when managing coronary complications in patients with BD. Both percutaneous and surgical options have been reported in the literature with variable outcomes. Multi-disciplinary team involvement is of utmost importance in order to offer a balanced therapeutic strategy to these patients. Further research is required to shed light to the unknowns surrounding this rare cohort.
20 Years of triple-valve surgery in the UK: demographic and outcome trends
Authors: Al-Zubaidi Fadi Ibrahim , Hussein Nabil , Smith Harry , Al-Adhami Ahmed , Sitaranjan Daniel , Caputo Massimo , Angelini Gianni D , Harky Amer , Vohra Hunaid Ahmed
Published: July 2024

OBJECTIVES

To describe evolving demographic trends and early outcomes in patients undergoing triple-valve surgery in the UK between 2000 and 2019.

METHODS

We planned a retrospective analysis of national registry data including patients undergoing triple-valve surgery for all aetiologies of disease. We excluded patients in a critical preoperative state and those with missing admission dates. The study cohort was split into 5 consecutive 4-year cohorts (groups A, B, C, D and E). The primary outcome was in-hospital mortality, and secondary outcomes included prolonged admission, re-exploration for bleeding, postoperative stroke and postoperative dialysis. Binary logistic regression models were used to establish independent predictors of mortality, stroke, postoperative dialysis and re-exploration for bleeding in this high-risk cohort.

RESULTS

We identified 1750 patients undergoing triple-valve surgery in the UK between 2000 and 2019. Triple valve surgery represents 3.1% of all patients in the dataset. Overall mean age of patients was 68.5 ± 12 years, having increased from 63 ±12 years in group A to 69 ± 12 years in group E (P < 0.001). Overall in-hospital mortality rate was 9%, dropping from 21% in group A to 7% in group E (P < 0.001). Overall rates of re-exploration for bleeding (11%, P = 0.308) and postoperative dialysis (11%, P = 0.066) remained high across the observed time period. Triple valve replacement, redo sternotomy and poor preoperative left ventricular ejection fraction emerged as strong independent predictors of mortality.

CONCLUSIONS

Triple-valve surgery remains rare in the UK. Early postoperative outcomes for triple valve surgery have improved over time. Redo sternotomy is a significant predictor of mortality. Attempts should be made to repair the mitral and/or tricuspid valves where technically possible.
Coercive Recruitment and Combatant Socialization: Reanalyzing the Role of Child Soldiering on Conflict-Related Sexual Violence
Authors: Ju Changwook
Published: July 2024

Why do armed organizations perpetrate conflict-related sexual violence (CRSV)? One prominent explanation focuses on the need to sustain group solidarity following the introduction of new combatants, a phenomenon referred to as combatant socialization. In this article, I revisit recent quantitative research suggesting that rebel groups recruiting children as soldiers engage in CRSV to facilitate combatant socialization. I argue that child soldiering without coercive recruitment does not, ipso facto, degrade internal cohesion and resilience; it is the use of coercion during recruitment that decimates intra-group solidarity and thereby necessitates CRSV for combatant socialization. Consequently, child soldiering per se should not induce rebel-perpetrated CRSV, whereas forced child recruitment does patently increase it. Zero-inflated ordered logit analysis confirms the differential implications of distinct modes of child recruitment for rebels’ combatant socialization via CRSV. This article highlights the centrality of coercive recruitment in CRSV occurrence and advances knowledge about combatant socialization and CRSV estimation.
Seismic structure of the Balmuccia Peridotite from a high-resolution refraction and reflection survey
Authors: Pasiecznik Damian , Greenwood Andrew , Bleibinhaus Florian , Hetényi György
Published: July 2024

In anticipation of a forthcoming scientific deep drilling initiative within the Western Alps near Balmuccia, Italy, a high-resolution seismic survey is performed at the proposed drill site. This site is situated within the Ivrea Verbano Zone (IVZ), characterized by lower crustal materials and fragments of upper-mantle rocks exposed adjacent to the Insubric Line. The 2-km-long seismic survey crosses an isolated km-scale outcrop of peridotite near the town of Balmuccia. Applying P-wave traveltime tomography, a substantial contrast in seismic velocities is identified, with velocities in the range of 1–8 km s−1. The peridotite displays velocities ranging from 6 to 8 km s−1. The higher velocities near 8 km s−1 are consistent with laboratory measurements on small-scale samples, while the low-velocity areas within the peridotite body reflect the influence of fractures and faults. The mean velocity derived for the peridotite body is ca. 7 km s−1. The reflection seismic analysis reveals subvertical reflectors positioned at the peridotite boundaries mapped at the surface, converging at a depth of ca. 0.175 km b.s.l. which images a lens-like structure for the peridotite body. However, the area beneath the imaged lens and the deeper Ivrea Geophysical Body (IGB) suggested by earlier studies is not well imaged, which leaves room for other interpretations regarding the relationship of these two bodies. Prior geophysical investigations provide only approximate depth estimates for the top of the IGB, spanning between 1–3 km depth b.s.l. Although the reflection data do not exhibit a series of continuous reflectors beneath the peridotite, a prominent reflection at ca. 1.3 km depth may indicate the top of the IGB.
Health promotion expectations and perceptions of sport club participants
Authors: Tézier Benjamin , Dogba Maman Joyce , Beck Valentin , Cossou Gbeto Inheldia , Vuillemin Anne , Lemonnier Fabienne , Rostan Florence , Guillemin Francis , Van Hoye Aurélie
Published: July 2024

To develop health promotion (HP) in sports clubs (SCs), stakeholders need to know the HP expectations of sports participants. However, the literature does not provide information on these aspects, which exacerbates the difficulty for SCs to provide an environment, activities and organization that promote health and to play the role entrusted to them in the integration of vulnerable populations. To fill this gap, this study explores the HP expectations and perceptions of sports participants, with a particular focus on ethnocultural characteristics, and documents participants’ understanding of HP. A descriptive qualitative study comprising semi-structured interviews was carried out with 22 French and Quebec sports participants. Because they have little experience with HP in their SC, participants do not seem to have many expectations of their SC in terms of HP. Nevertheless, they felt that SCs can play an important role in health and suggested several themes and types of action, such as seminars on nutrition, activities outside the SC to develop cohesion or health monitoring. Sports participants from ethnocultural minorities seem to appreciate the programs designed to integrate them. There is a predominantly physical conception of health and the contribution of SCs to health, and the relationship between the types of health determinants (economic, environmental, organizational and social) and health is not clear. This study shows that the idea of a health-promoting SC appeals to SC participants, but this approach has not yet taken root in this setting or in society as a whole.
Mismanagement and misinterpretations in asylum interviews: Perspectives from South Africa and Sweden
Authors: Ottosson Lisa , Angu Pineteh , Gustafsson Kristina
Published: July 2024

This article explores the interactions between key actors in asylum interviews in South Africa and Sweden. It is based on forty-one interviews with asylum seekers, interpreters, state officials, and legal representatives. The analysis is guided by theories on professional encounters, bureaucratic violence, and interdependence. The result is presented in two themes: the emergence of mismanagement due to repressive policies and cost-cutting measures, and misinterpretation due to poor interpretation services and failure to recognize the hermeneutic aspects of asylum seekers’ claims. These issues lead to mistrust in the asylum system and in each other’s capacities, as key actors fail to take joint responsibility for the interview act and its outcome. The conclusion is that all key actors operate within a destructive process of mistrust, reinforced by an increasingly repressive political framework as its strongest driving force.
Self-generated asylum evidence: Scripting, staging and desperation in the assessment process
Authors: Laws Ben
Published: July 2024

The demonstrable rise in self-generated asylum evidence—most typically via social media—is in need of explication. Drawing on cases from ethnographic research in Sweden this article sets out to understand why asylum seekers turn to extreme forms of activity such as filming themselves burning the Quran. It appears that such ‘staged’ evidence is most often born out of a sense of emotional desperation in the face of a stone-wall assessment system which leans heavily towards rejection. To reach this conclusion, however, the article first engages with more traditional asylum ‘scripts’ and roadmaps endorsed and shaped by NGO’s and legal practitioners. The 2015 Migration Crisis in Europe has fundamentally altered the assessment process, not only in its ‘bar-raising’ aspects for positive decisions, but also by reconfiguring the very form and structure of evidence presented.
More than a number: Exploring the impact of age(ing) on refugees’ experiences of arrival
Authors: Enßle-Reinhardt Friederike
Published: July 2024

Age(ing) as an intersectional category has seen only limited attention in refugee studies so far. Although research exists on the living situation and vulnerabilities of specific age groups, conceptual perspectives on how age(ing), as a factor of difference, plays out in refugees’ experiences of flight and arrival has been explored to a lesser extent. Drawing on qualitative research with fifty-three refugees who arrived in Germany since 2015 this contribution explores refugees’ experiences of arrival and their interrelation with their life courses. The analysis follows an intersectional life course perspective to unpack arrival experiences through the dimensions of key life events and their timing; locally and globally linked lives; categories of difference; as well as systems of domination and refugees’ agency. The contribution closes by proposing three conceptual considerations about how a focus on age(ing) can enhance a nuanced understanding of forced migrants’ living experiences.
A probiotic NVP1704 alleviates stress-induced sleeplessness/depression-like symptoms in mice by upregulating serotonergic and GABAergic systems and downregulating NF-κB activation
Authors: Baek Ji-Su , Lee Dong-Yun , Han Seung-Won , Kim Dong-Hyun
Published: July 2024

Sleeplessness (insomnia) is a potential symptom of depression. A probiotic NVP1704 alleviates depression-like behavior and neuroinflammation in mice. Therefore, to understand whether NVP1704 could be effective against sleeplessness in vivo, we exposed immobilization stress (IS) in mice, then orally administered NVP1704 for 5 days, and assayed depression/anxiety-like behavior in the open field, elevated plus maze, and tail suspension tests, sleeping latency time, and sleep duration, euthanized then by exposure to CO2, and analyzed their related biomarkers. Oral administration of NVP1704 decreased IS-induced depression/anxiety-like behavior and sleeping latency time and increased IS-suppressed sleeping duration. NVP1704 increased IS-suppressed expression of γ-aminobutyric acid (GABA), GABAA receptor α1 (GABAARα1) and α2 subunits (GABAARα2), serotonin, 5-HT receptors (5-HT1AR and 5-HT1BR), and melatonin receptors (MT1R and MT2R) in the prefrontal cortex and thalamus. NVP1704 also increased the IS-suppressed GABAARα1-positive cell population in the prefrontal cortex and decreased IS-induced corticosterone, TNF-α, and IL-6 expression and the NF-κB+Iba1+ cell population in the brain and myeloperoxidase, TNF-α, and IL-6 expression and the NF-κB+CD11c+ cell population in the colon. Based on these findings, NVP1704 may alleviate depression/anxiety/sleeplessness-like behaviors through the upregulation of serotonergic and GABAergic systems and downregulation of NF-κB activation.
Dual quantitative PCR assays for the rapid detection of Trichophyton indotineae from clinical samples
Authors: Baron Audrey , Hamane Samia , Gits-Muselli Maud , Legendre Lina , Benderdouche Mazouz , Mingui Anselme , Ghelfenstein-Ferreira Théo , Alanio Alexandre , Dellière Sarah
Published: July 2024

Trichophyton indotineae is an emerging species of the Trichophyton mentagrophytes complex (TMC), responsible for an epidemic of widespread hairless skin infections that is frequently (50–70%) resistant to terbinafine. In order to initiate appropriate treatment as quickly as possible without waiting for culture positivity (10–15 days) and molecular identification from the strain, we developed a dual quantitative PCR (qPCR) for the direct detection of T. indotineae in clinical samples. We first designed a T. indotineae-specific qPCR assay (TI-qPCR) targeting a single specific polymorphism in the internal transcribed spacer region. Although none of the 94 non-dermatophyte and 7 dermatophyte species were amplified, this TI-qPCR allowed amplification of other TMC species at a lower yield. With equal amounts (0.1 ng) of DNA per reaction, the mean quantitative cycle (Cq) values for T. indotineae and non-indotineae TMC were 27.9 (±0.1) and 38.9 (±0.3), respectively. Therefore, we normalized this assay against a previously validated pan-dermatophyte qPCR assay (PD-qPCR) and relied on the ΔCq [(TI-qPCR) − (PD-qPCR)] to identify T. indotineae versus other TMC species. Dual assay was validated using 86 clinical samples of culture-confirmed T. indotinea and 19 non-indotineae TMC cases. The mean ΔCq for non-indotineae TMC was 9.6 ± 2.7, whereas the ΔCq for T. indotinea was −1.46 ± 2.1 (P < .001). Setting the ΔCq at 4.5 as a cutoff value resulted in 100% specificity for the detection of T. indotineae. This dual qPCR assay quickly detects T. indotineae from skin scrapings, aiding in early diagnosis and treatment for patients with suspected infection.
Parallel Evolution in Mosquito Vectors—A Duplicated Esterase Locus is Associated With Resistance to Pirimiphos-methyl in Anopheles gambiae
Authors: Nagi Sanjay C , Lucas Eric R , Egyir-Yawson Alexander , Essandoh John , Dadzie Samuel , Chabi Joseph , Djogbénou Luc S , Medjigbodo Adandé A , Edi Constant V , Ketoh Guillaume K , Koudou Benjamin G , Ashraf Faisal , Clarkson Chris S , Miles Alistair , Weetman David , Donnelly Martin J
Published: July 2024

The primary control methods for the African malaria mosquito, Anopheles gambiae, are based on insecticidal interventions. Emerging resistance to these compounds is therefore of major concern to malaria control programs. The organophosphate (OP), pirimiphos-methyl, is a relatively new chemical in the vector control armory but is now widely used in indoor-residual spray campaigns. While generally effective, phenotypic resistance has developed in some areas in malaria vectors. Here, we used a population genomic approach to identify novel mechanisms of resistance to pirimiphos-methyl in A. gambiae s.l mosquitoes. In multiple populations, we found large and repeated signals of selection at a locus containing a cluster of detoxification enzymes, some of whose orthologs are known to confer resistance to OPs in Culex pipiens. Close examination revealed a pair of alpha-esterases, Coeae1f and Coeae2f, and a complex and diverse pattern of haplotypes under selection in A. gambiae, A. coluzzii and A. arabiensis. As in C. pipiens, copy number variants have arisen at this locus. We used diplotype clustering to examine whether these signals arise from parallel evolution or adaptive introgression. Using whole-genome sequenced phenotyped samples, we found that in West Africa, a copy number variant in A. gambiae is associated with resistance to pirimiphos-methyl. Overall, we demonstrate a striking example of contemporary parallel evolution which has important implications for malaria control programs.
Limitations of current high-throughput sequencing technologies lead to biased expression estimates of endogenous retroviral elements
Authors: Kitsou Konstantina , Katzourakis Aris , Magiorkinis Gkikas
Published: July 2024

Human endogenous retroviruses (HERVs), the remnants of ancient germline retroviral integrations, comprise almost 8% of the human genome. The elucidation of their biological roles is hampered by our inability to link HERV mRNA and protein production with specific HERV loci. To solve the riddle of the integration-specific RNA expression of HERVs, several bioinformatics approaches have been proposed; however, no single process seems to yield optimal results due to the repetitiveness of HERV integrations. The performance of existing data-bioinformatics pipelines has been evaluated against real world datasets whose true expression profile is unknown, thus the accuracy of widely-used approaches remains unclear. Here, we simulated mRNA production from specific HERV integrations to evaluate second and third generation sequencing technologies along with widely used bioinformatic approaches to estimate the accuracy in describing integration-specific expression. We demonstrate that, while a HERV-family approach offers accurate results, per-integration analyses of HERV expression suffer from substantial expression bias, which is only partially mitigated by algorithms developed for calculating the per-integration HERV expression, and is more pronounced in recent integrations. Hence, this bias could erroneously result into biologically meaningful inferences. Finally, we demonstrate the merits of accurate long-read high-throughput sequencing technologies in the resolution of per-locus HERV expression.
Impact of relative cisplatin dose to skeletal muscle mass on adverse events in patients with head and neck cancer undergoing chemoradiotherapy
Authors: Suzuki Satoshi , Yokota Tomoya , Notsu Akifumi , Hamauchi Satoshi , Onozawa Yusuke , Fushiki Kunihiro , Oshima Kotoe , Kawakami Takeshi , Tsushima Takahiro , Yasui Hirofumi , Ogawa Hirofumi , Onoe Tsuyoshi , Kawatani Keisuke , Yamazaki Kentaro
Published: July 2024

Background

Chemoradiotherapy (CRT) with high-dose cisplatin (CDDP) is the standard treatment for locally advanced head and neck squamous cell carcinoma (HNSCC). Although dosing is based on body surface area (BSA), some patients experience CDDP-related adverse events (AEs). We aimed to evaluate the impact of relative CDDP dose to skeletal muscle mass (SMM) on chemotherapy-associated AEs in patients with HNSCC undergoing CRT with high-dose CDDP.

Materials and Methods

We retrospectively analyzed data of patients who underwent CRT with high-dose CDDP (80-100 mg/m2, triweekly) between 2010 and 2023. SMM was measured as the cross-sectional muscle area at the third cervical vertebra (C3-SMM) using computed tomography; the skeletal muscle index (SMI) was defined as SMM normalized by squared height. The CDDP index was defined as the prescribed CDDP dose divided by SMI. CDDP-related AEs were assessed during the first cycle using Common Terminology Criteria for Adverse Events v5.0.

Results

Overall, 306 patients were identified. The CDDP index cutoff value best associated with grade ≥ 3 AEs was 10.312. Grade ≥ 3 hematological toxicities exhibited stronger association with high CDDP index value than with low CDDP index value (26.9% vs 16.3%, P = .033). Multivariate analysis revealed that high CDDP index value and creatinine clearance < 70 mL/minute were predictive factors for grade ≥ 3 AEs (odds ratio [OR] 2.55, P = .008; OR 3.68, P = .002, respectively).

Conclusion

The CDDP index based on C3-SMM was an independent predictive factor for grade ≥ 3 CDDP-related AEs. C3-SMM is potentially more useful than BSA for determining the optimal CDDP dose in patients with HNSCC.
Activity and Participation Are Associated With Future Falls, Hospitalizations, and Emergency Visits in Community-Dwelling Older Adults
Authors: Klatt Brooke N , Perera Subashan , Dunlap Pamela M , Rosso Andrea L , Brach Jennifer S
Published: July 2024

Objective

Activity and participation are important for older adults as they are associated with well-being and quality of life. Falls, emergency department (ED) visits, and hospitalizations are adverse health outcomes that impact older adults. Limited research has investigated whether measurement of activity and participation are related to adverse health events in community dwelling older adults. This study sought to examine the association between activity and participation with falls, ED visits, and hospitalization over 1 year in community dwelling older adults.

Methods

A secondary analysis of a longitudinal clinical trial of 341 community dwelling older adults was conducted. The sample mean age was 80.9 (SD = 7.7) years and 83% were female. One-year risk of falls was associated with baseline Late Life Function and Disability Instrument (LLFDI) components of overall function and disability (frequency and limitations dimensions). Incident rate ratios (IRRs) and 95% CIs were calculated.

Results

For each five-point higher score (clinically meaningful difference) in activity as measured by LLFDI-overall function (adjusted for age, race, sex, comorbidities and fall history), there was an 18% lower rate of falls (IRR = 0.82, 95% CI = 0.74–0.92), 12% reduction in hospitalizations (IRR = 0.88; 95% CI = 0.77–0.99), and 11% lower rate of emergency room visits (IRR = 0.89, 95% CI = 0.81–0.98). Greater participation as measured by the LLFDI limitations dimension was related to fewer falls (IRR = 0.93, 95% CI = 0.87–1.00) and hospitalizations (IRR = 0.91, 95% CI = 0.83–0.99).

Conclusion

Greater activity and participation are associated with a lower incidence of falls, ED visits, and hospitalizations representing an important consideration for targeted physical therapist interventions.

Impact Statement

Physical therapists are uniquely positioned to identify and address reduced activity and participation. If activity and participation are specifically targeted and improved through physical therapy, undesirable distal health outcomes might be prevented or minimized.

Lay Summary

Greater activity and participation were found to be related to lower rate of falls, ED visits, and hospitalizations in a sample of 341 older adults who lived in the community.
Risk factors for positive post-transplantation measurable residual disease in patients with acute lymphoblastic leukemia
Authors: Wang Yuewen , Fu Guomei , Xu Lanping , Wang Yu , Cheng Yifei , Zhang Yuanyuan , Zhang Xiaohui , Liu Yanrong , Liu Kaiyan , Huang Xiaojun , Chang Yingjun
Published: July 2024

Background:

The level of measurable residual disease (MRD) before and after transplantation is related to inferior transplant outcomes, and post-hematopoietic stem cell transplantation measurable residual disease (post-HSCT MRD) has higher prognostic value in determining risk than pre-hematopoietic stem cell transplantation measurable residual disease (pre-HSCT MRD). However, only a few work has been devoted to the risk factors for positive post-HSCT MRD in patients with acute lymphoblastic leukemia (ALL). This study evaluated the risk factors for post-HSCT MRD positivity in patients with ALL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods:

A total of 1683 ALL patients from Peking University People’s Hospital between January 2009 and December 2019 were enrolled to evaluate the cumulative incidence of post-HSCT MRD. Cox proportional hazard regression models were built for time-to-event outcomes. Multivariate analysis was performed to determine independent influencing factors from the univariate analysis.

Results:

Both in total patients and in T-cell ALL or B-cell ALL, pediatric or adult, human leukocyte antigen-matched sibling donor transplantation or haploidentical SCT subgroups, positive pre-HSCT MRD was a risk factor for post-HSCT MRD positivity (P <0.001 for all). Disease status (complete remission 1 [CR1] vs. ≥CR2) was also a risk factor for post-HSCT MRD positivity in all patients and in the B cell-ALL, pediatric, or haploidentical SCT subgroups (P = 0.027; P = 0.003; P = 0.035; P = 0.003, respectively). A risk score for post-HSCT MRD positivity was developed using the variables pre-HSCT MRD and disease status. The cumulative incidence of post-HSCT MRD positivity was 12.3%, 25.1%, and 38.8% for subjects with scores of 0, 1, and 2–3, respectively (P <0.001). Multivariate analysis confirmed the association of the risk score with the cumulative incidence of post-HSCT MRD positivity and relapse as well as leukemia-free survival and overall survival.

Conclusion:

Our results indicated that positive pre-MRD and disease status were two independent risk factors for post-HSCT MRD positivity in patients with ALL who underwent allo-HSCT.
The Bittersweet Reality: The Cardiovascular Risk of Artificial Sweeteners
Authors: Yeterian Mesrob , Parikh Manish A. , Frishman William H. , Peterson Stephen J.
Published: July 2024

Artificial sweeteners are increasingly popular as alternatives to sugar. Approximately 41% of the American adult population reports regular consumption of low-calorie sweeteners. People are not even aware they are ingesting artificial sweeteners as they are now in chewing gum, toothpaste, various food products, baked goods, and even pharmaceutical products. Some of these sweeteners are sweeter than sugar, some less sweet than sugar, and some are natural sweeteners. With the goal of increasing palatability, many products have multiple additives to create the perfect taste. Despite their widespread use and perceived benefits, there is increasing concern in the academic community about the long-term safety of these artificial sweeteners and their role in increasing the burden of cardiovascular diseases, including coronary heart disease, stroke, and heart failure. There is general agreement about the cardiovascular risk of added sugars to a diet. Public health authorities have recommended limiting added sugar consumption. Replacing sugar with these artificial sweeteners has become increasingly popular, but safety remains a question. While multiple well-designed randomized clinical trials are needed for the conclusion, review of the current literature gives us pause about the cardiovascular risk and long-term safety of these additives.
Effect of Astigmatism Treatment With Three Excimer Lasers After Photorefractive Keratectomy
Authors: Sedaghat Mohammad-Reza , Sadeghi Javad , Varshovi-Jaghargh Iman , Heravian Javad , Belin Michael W. , Momeni-Moghaddam Hamed
Published: July 2024

Objectives:

To compare astigmatism correction after photorefractive keratectomy (PRK) using three excimer laser devices, Alcon Wavelight EX500, Schwind Amaris 1,050, and Technolas Teneo317 M2.

Methods:

This retrospective study included 414 eyes from 414 subjects with a history of PRK performed using Alcon Wavelight (n=172), Schwind Amaris (n=122), and Technolas (n=120). Uncorrected & corrected distance visual acuity (UDVA & CDVA), and refractive status (spherical equivalent (SE) and vector analysis (J0 and J45)) were postoperatively recorded at the 6-month and 12-month examinations.

Results:

The mean CDVA and J45 at 6-month and 12-month showed no statistically significant difference among the three different excimer lasers (P>0.05). There was a statistically significant difference in mean UDVA and J0 at 6-month and 12-month after PRK among the three groups, with no statistically significant difference between Alcon Wavelight and Schwind Amaris lasers, while both of the prior lasers showed a significant difference with the Technolas laser. The highest and lowest changes in the magnitude of J0 in 6-month and 12-month follow-ups were seen for the Alcon Wavelight and Technolas groups, respectively. Both Schwind Amaris and Technolas had a small hyperopic SE while the Alcon Wavelight's SE was minimally myopic. This difference in SE between Alcon Wavelight and both Schwind Amaris and Technolas reached statistical significance.

Conclusion:

While all three lasers performed well in reducing preoperative astigmatism; however, the Alcon Wavelight and Schwind Amaris were more effective in correcting astigmatism than the Technolas. The difference between the Alcon Wavelight and Schwind Amaris did not reach statistical significance.
Characterization of chronic pain, pain interference, and daily pain experiences in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study
Authors: Alberts Nicole M. , Leisenring Wendy , Whitton Jillian , Stratton Kayla , Jibb Lindsay , Flynn Jessica , Pizzo Alex , Brinkman Tara M. , Birnie Kathryn , Gibson Todd M. , McDonald Aaron , Ford James , Olgin Jeffrey E. , Nathan Paul C. , Stinson Jennifer N. , Armstrong Gregory T.
Published: July 2024

Although survivors of childhood cancer are at an increased risk, little is known about the prevalence of chronic pain, associated interference, and daily pain experiences. Survivors (N = 233; mean age = 40.8 years, range 22-64 years; mean time since diagnosis = 32.7 years) from the Childhood Cancer Survivor Study completed pain and psychosocial measures. Survivors with chronic pain completed 2-week, daily measures assessing pain and psychological symptoms using mHealth-based ecological momentary assessment. Multivariable-modified Poisson and linear regression models estimated prevalence ratio estimates (PR) and mean effects with 95% confidence intervals (CI) for associations of key risk factors with chronic pain and pain interference, respectively. Multilevel mixed models examined outcomes of daily pain and pain interference with prior day symptoms. Ninety-six survivors (41%) reported chronic pain, of whom 23 (24%) had severe interference. Chronic pain was associated with previous intravenous methotrexate treatment (PR = 1.6, 95% CI 1.1-2.3), respiratory (PR = 1.8, 95% CI 1.2-2.5), gastrointestinal (PR = 1.6, 95% CI 11.0-2.3), and neurological (PR = 1.5, 95% CI 1.0-2.1) chronic health conditions, unemployment (PR = 1.4, 95% CI 1.0-1.9) and clinically significant depression and anxiety (PR = 2.9, 95% CI 2.0-4.2), as well as a diagnosis of childhood Ewing sarcoma or osteosarcoma (PR = 1.9, 95% CI 1.0-3.5). Higher pain interference was associated with cardiovascular and neurological conditions, unemployment and clinical levels of depression and/or anxiety, and fear of cancer recurrence. For male, but not female survivors, low sleep quality, elevated anxiety, and elevated depression predicted high pain intensity and interference the next day. A substantial proportion of childhood cancer survivors experience chronic pain and significant associated interference. Chronic pain should be routinely evaluated, and interventions are needed.