bluuebunny/crossref_metadata_2025_split huggingface dataset:
Importin α inhibitors act against the differentiated stages of apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii
Authors: Bhambid Manasi , Walunj Sujata B , Anupama C A , Jain Shilpi , Mehta Diksha , Arya Anjali , Wagstaff Kylie M , Panda Ashutosh , Jans David A , Mohmmed Asif , Patankar Swati 
Published: December 2024

Abstract

Background
Nuclear import, dependent on the transporter importin α (IMPα), is a drug target for apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii. Indeed, a panel of small molecule inhibit interactions between IMPα and nuclear localization signals (NLSs) in vitro and the growth of rapidly dividing stages (P. falciparum blood stages and T. gondii tachyzoites) in culture.

Objectives
As new drugs targeting multiple life cycle stages of both parasites are required, the panel of IMPα inhibitors was tested for their ability to inhibit nuclear transport in the rapidly dividing stages and the maturation of differentiated stages (P. falciparum gametocytes and T. gondii bradyzoites).

Methods
Using biophysical assays, Bay 11-7082, a Bay 11-7085 structural analogue, was tested for inhibition of IMPα:NLS interactions. The effect of the panel of inhibitors on the nuclear localization of reporter proteins was analysed in both parasites using transfections and microscopy. Also, using microscopy, the effect of inhibitors on differentiated stages of both parasites was tested.

Results
Bay 11-7085 can inhibit nuclear transport in tachyzoites, while GW5074 and Caffeic Acid Phenethyl Ester (CAPE) can inhibit nuclear transport in the blood stages. Interestingly, CAPE can strongly inhibit gametocyte maturation, and Bay 11-7082 and Bay 11-7085 weakly inhibit bradyzoite differentiation.

Conclusions
As differentiation of gametocytes and bradyzoites is dependent on the activation of gene expression triggered by the nuclear translocation of transcription factors, our work provides a ‘proof of concept’ that targeting nuclear import is a viable strategy for the development of therapeutics against multiple stages of apicomplexan parasites, some of which are recalcitrant to existing drugs.
Comparing Refrigeration to Immediate Room Temperature Testing for Uric Acid Monitoring in Rasburicase-Treated Patients
Authors: Lin Leo , Filtz Michael , Wilson Jeffrey , Errigo Roscoe , Zuromski Lauren M , Nguyen Sorenson Anh , Young Brittany A 
Published: December 2024

Abstract

Background
Rasburicase retains activity at room temperature (RT), so specimens collected for uric acid-level monitoring require cooling protocols. Our objective was to determine if we could ease these preanalytical requirements to improve compliance while maintaining accuracy.

Methods
Fifty pairs of specimens were transported and stored either on ice or at RT. All were tested at 3 time points postcollection: immediately upon arrival to the laboratory (approximately 45 min), 90, and 135 min.

Results
Uric acid concentrations are not clinically significantly different in RT or iced specimens, as long as specimens are tested within approximately 45 min postcollection. There was a negative bias in uric acid levels in a subset of specimens if they were held at RT and tested at 90 min (−9.1%) and 135 min (−17.5%). Specimens tested within 2 rasburicase half-lives postinfusion have an additional 24% decrease in uric acid levels if kept at RT for 90 min. Specimens from patients given a 6 mg dose had an 18% decrease in uric acid concentration compared to a 3 mg dose.

Conclusions
Laboratories that can test uric acid levels rapidly after specimen collection may be able to validate alternative preanalytical methods to transporting and testing on ice.
H and B Blood Antigens Are Essential for In Vitro Replication of GII.2 Human Norovirus
Authors: Tamiya Shigeyuki , Matsumoto Naomi , Kurokawa Shiho , Nakamura Yutaka , Takahashi Yu , Sakon Naomi , Inoue Mikihiro , Koike Yuhki , Uchida Keiichi , Yuki Yoshikazu , Ushijima Hiroshi , Kiyono Hiroshi , Sato Shintaro 
Published: December 2024

Abstract

Background
Human norovirus (HuNoV) is a major cause of enteric infectious gastroenteritis and is classified into several genotypes based on its capsid protein amino acid sequence and nucleotide sequence of the polymerase gene. Among these, GII.4 is the major genotype worldwide. Epidemiological studies have highlighted the prevalence of GII.2. Although recent advances using human tissue– and induced pluripotent stem cell (iPSC)–derived intestinal epithelial cells (IECs) have enabled in vitro replication of multiple HuNoV genotypes, GII.2 HuNoV could replicate only in tissue-derived IECs and not in iPSC-derived IECs.

Methods
We investigated the factors influencing GII.2 HuNoV replication in IECs, focusing on histo-blood group antigens. We also assessed the immunogenicity of GII.2 virus-like particles (VLPs) and their ability to induce neutralizing antibodies. Antibody cross-reactivity was tested to determine whether GII.2 VLPs could neutralize other HuNoV genotypes, including GII.4, GII.3, GII.6, and GII.17.

Results
Our findings indicated that GII.2 HuNoV replication in vitro requires the presence of both H and B antigens. Moreover, GII.2 VLPs generated neutralizing antibodies effective against both GII.2 and GII.4 but not against GII.3, GII.6, or GII.17. Comparatively, GII.2 and GII.17 VLPs induced broader neutralizing responses than GII.4 VLPs.

Conclusions
The findings of this study suggests that GII.2 and GII.17 VLPs may be advantageous as HuNoV vaccine candidates because they elicit neutralizing antibodies against the predominant GII.4 genotype, which could be particularly beneficial for infants without prior HuNoV exposure. These insights will contribute to the development of effective HuNoV vaccines.
Synthesizing Attachment Theory with the REBUS Model
Authors: Cherniak Aaron D. , Carhart-Harris Robin , Gruneau Brulin Joel , Mikulincer Mario , Östlind Sebastian , Granqvist Pehr 
Published: December 2024

Abstract
In this chapter, the authors synthesize the relational developmental perspective of attachment theory with a neuroscientific model: the RElaxed Beliefs Under pSychedelics (REBUS). This synthesis, the authors argue, can serve as an organizing framework for psychedelic science. Attachment theory posits that people develop internal working models (IWMs) of relational experiences with close others. These IWMs function as predictive models (“priors”) that, for better and for worse, contribute to people’s social and emotional worlds and organize how they navigate them. Effective psychedelic interventions may work by inducing a hyper-plastic neural state that, supported by corrective relational experiences (with therapists, God, or others), facilitates rapid and deep learning. This can include revision of IWMs toward greater security and other psychological transformations. Based on the attachment-REBUS synthesis, the authors describe three main proposals to guide future research. First, individual differences in attachment security predict the phenomenology of psychedelic experiences and processes related to their integration. Second, increasing attachment security may be a clinical outcome of efficacious psychedelic therapy. Third, among other process-level mechanisms, the clinical utility of psychedelic treatment involves attachment-related dynamics (e.g., connectedness to others and God, alleviation of attachment-related worries and defenses). Finally, the authors provide words of caution and future directions.
Gesture and Agency in Musical Performance
Authors: Montague Eugene 
Published: December 2024

Abstract
This chapter explores relationships between gesture and agency in musical performance, using the physical movements executed by performers as primary points of reference. It draws on two separate definitions of agency, from neuroscience and phenomenology, respectively. From these bases, the chapter examines how the movements of by performers may accrue additional relevance and meaning, and in the process can become seen and heard as gestures by both audience and musicians alike. Through such encounters with gesture in the contexts of performances, music serves as a location for the creation and communication of human agency. To support this argument, and give concrete examples of this process, the chapter analyzes videos and sound from performances by pianists Krystian Zimerman and Brad Mehldau. These case studies illustrate the potential provided by the connection between gesture and agency to deepen our understanding of the experience of musical performances and the activity of musical performers.
Beyond the National Paradigm
Authors: Burdett Charles , Polezzi Loredana 
Published: December 2024

Abstract
This chapter discusses the impact of a combined transnational and translational methodology on definitions of “Italian literature” and on the critical reading practices that inform the approach to literary texts. It calls into question assumptions of geographic, cultural, or linguistic homogeneity and their historical role in defining an Italian literary canon as well as ideas of “Italianness,” arguing instead in favor of a more fluid and inclusive notion of “Italian literature.” Using examples that range from colonial and postcolonial to diasporic and translingual writing, as well as recent (re)translations of classics, the article aims to illustrate the porous nature of the production, circulation, and reception of literary works, as well as the political nature of all acts of reading. It suggests how a transnational and translational approach to literature promotes a reading experience that is consonant with the complex interweaving of cultures that characterizes the realities in which we live.
Emotional Governance and Authoritarian Populism
Authors: Kinnvall Catarina 
Published: December 2024

Abstract
This chapter addresses the role of emotions for authoritarian populism and governance. It discusses how narratives of past practices, memories, and symbols become emotional, embodied, and material representations to which individuals and groups attach a sense of self and purpose. It also discusses how such narratives become avenues for elites to create and emotionally govern borders and boundaries around constructions of collective identities. The chapter provides a detailed understanding of how emotions, values, identities, experiences, and political beliefs are interrelated, as well as the structural, socioeconomic, and institutional conditions that underlie such relations at national and transnational levels. It provides a comprehensive account of authoritarian populism and its emotional ramifications in contemporary political contexts, with some illustrative examples from India, Russia, and Sweden.
Species- and organ-specific contribution of peroxisomal cinnamate:CoA ligases to benzoic and salicylic acid biosynthesis
Authors: Wang Yukang , Miao Huiying , Qiu Jiehua , Liu Menghui , Jin Gaochen , Zhang Wenxuan , Song Shuyan , Fan Pengxiang , Xin Xiufang , Hu Jianping , Li Ran , Pan Ronghui 
Published: December 2024

Abstract
Salicylic acid (SA) is a prominent defense hormone whose basal level, organ-specific accumulation, and physiological role vary widely among plant species. Of the 2 known pathways of plant SA biosynthesis, the phenylalanine ammonia lyase (PAL) pathway is more ancient and universal but its biosynthetic and physiological roles in diverse plant species remain unclear. Studies in which the PAL pathway is specifically or completely inhibited, as well as a direct comparison of diverse species and different organs within the same species, are needed. To this end, we analyzed the PAL pathway in rice (Oryza sativa) and Arabidopsis (Arabidopsis thaliana), 2 distantly related model plants whose basal SA levels and distributions differ tremendously at the organism and tissue levels. Based on our recent identification of the rice peroxisomal cinnamate:CoA ligases (CNLs), we identified 2 peroxisomal CNLs from Arabidopsis and showed CNL as the most functionally specific enzyme among the known enzymes of the PAL pathway. We then revealed the species- and organ-specific contribution of the PAL pathway to benzoic and salicylic acid biosynthesis and clarified its physiological importance in rice and Arabidopsis. Our findings highlight the necessity to consider species and organ types in future SA-related studies and may help to breed new disease-resistant crops.
Modeling of randomized hepatitis C vaccine trials: Bridging the gap between controlled human infection models and real-word testing
Authors: Mackesy-Amiti Mary-Ellen , Gutfraind Alexander , Tatara Eric , Collier Nicholson T , Cotler Scott J , Page Kimberly , Ozik Jonathan , Boodram Basmattee , Major Marian , Dahari Harel 
Published: December 2024

Abstract
Global elimination of chronic hepatitis C (CHC) remains difficult without an effective vaccine. Since injection drug use is the leading cause of hepatitis C virus (HCV) transmission in Western Europe and North America, people who inject drugs (PWID) are an important population for testing HCV vaccine effectiveness in randomized-clinical trials (RCTs). However, RCTs in PWID are inherently challenging. To accelerate vaccine development, controlled human infection (CHI) models have been suggested as a means to identify effective vaccines. To bridge the gap between CHI models and real-world testing, we developed an agent-based model simulating a two-dose vaccine to prevent CHC in PWID, representing 32,000 PWID in metropolitan Chicago and accounting for networks and HCV infections. We ran 500 trial simulations under 50 and 75% assumed vaccine efficacy (aVE) and sampled HCV infection status of recruited in silico PWID. The mean estimated vaccine efficacy (eVE) for 50 and 75% aVE was 48% (SD ± 12) and 72% (SD ± 11), respectively. For both conditions, the majority of trials (∼71%) resulted in eVEs within 1 SD of the mean, demonstrating a robust trial design. Trials that resulted in eVEs &gt;1 SD from the mean (lowest eVEs of 3 and 35% for 50 and 75% aVE, respectively), were more likely to have imbalances in acute infection rates across trial arms. Modeling indicates robust trial design and high success rates of finding vaccines to be effective in real-life trials in PWID. However, with less effective vaccines (aVEs∼50%) there remains a higher risk of concluding poor vaccine efficacy due to post-randomization imbalances.
Bidirectional links between sleep and pain among heavy-drinking veterans with insomnia
Authors: Tracy Eunjin Lee , So Christine J , Shoemaker Sydney D , Kanaley Jill A , Trull Timothy , Manrique-Acevedo Camila , McCrae Christina S , Borsari Brian , Miller Mary Beth 
Published: December 2024

Abstract

Study Objectives
Military veterans often suffer from chronic pain and sleep issues at a greater frequency than the general population, leading some to self-medicate with alcohol. While research shows a connection between sleep and pain, few studies have examined bidirectional links between sleep and pain at the daily level—or the extent to which alcohol use may moderate these associations.

Methods
Heavy-drinking veterans seeking treatment for insomnia (N = 109, 82.5% male, mean age 38.9 years) completed 14 days of morning diaries documenting sleep patterns, pain intensity, and alcohol consumption. Multilevel modeling examined within- and between-person associations between sleep (quality, duration, and efficiency) and next-day pain as well as pain and same-night sleep.

Results
Individuals with longer sleep duration, better sleep quality, and higher sleep efficiency (SE) reported lower pain levels compared to those with shorter sleep, poorer sleep quality, and lower SE (p values &lt;.001 to .01). In addition, on days when individuals experienced better sleep quality compared to their own average, they reported lower pain levels the following day (p = .01). In contrast to hypotheses, daily pain levels did not predict sleep outcomes at the daily within-person level, although significant between-person correlations were noted. Daily alcohol intake did not affect these relationships.

Conclusions
Sleep quality is associated with the daily experience of pain among heavy-drinking veterans with insomnia. Daily variations in sleep quality significantly impact pain, irrespective of alcohol consumption, highlighting a predominantly unidirectional influence from sleep to pain. These findings underscore the importance of optimizing sleep to mitigate pain in this population.
A Multi-scalar Feminist Project for a Care Right: Angles for a Deepening Understanding
Authors: Torres Santana Ailynn 
Published: December 2024

Abstract
Guarantees of the right to care, decent working conditions, and co-responsibility in the exercise of care continue to be disputed. The areas where these disputes occur are key to understanding the extent to which there are windows of opportunity for a dignified life. This article analyzes critical angles for understanding the multi-scalar feminist political action in Latin America to advance the guarantees of the right to care. Dimensions related to states, feminist political action, contradictions within care policy, the relevance of Latin American theorization of care, and the challenges posed by the retraditionalization of care in the current context are mentioned.
Determination of pesticide residues in bee honey and pollen grains with their potential human health risks in the Nile Delta, Egypt
Authors: Abd-Alla Asmaa El-Metwally , Salem Rasha Adel , Amro Abdulraouf Mohamed 
Published: December 2024

Abstract
A growing trend in understanding human health involves looking at the bigger picture by examining all potential environmental exposures that may cause health risks, with a particular focus on dietary intake of anthropogenic chemicals. This study investigated the presence of pesticide residues in honey and pollen samples collected randomly from ten locations in four agricultural governorates during the spring season of 2023 in the Nile Delta, Egypt. A QuEChERS extraction was employed for sample preparation before GC–MS analysis for pesticide residues. The human health risk associated with these residues were evaluated using hazard quotient (HQ). Our findings indicate that the detection rate and levels of pesticide residues are greater than previously reported. Giza governorate exhibited the highest content of residues in both honey and pollen samples, followed by El-Dakahlia, El-Qalyubia and Gharbia. Also, honey samples from El-Dakahlia, El-Qalyubia, and Giza contained the highest concentrations of aldrin, hexachlorocyclohexane (HCH) and chlorpyrifos, ranging from 10.45 to 19.6 μg kg−1, 21.70 to 62.23 μg kg−1, and 167.55 to 190.74 μg kg−1, respectively. Pollen grain samples from Giza and El-Dakahlia showed high levels of chlorpyrifos (76.20 μg kg−1) and HCH (33.60 μg kg−1), respectively. Health hazard and quotient studies indicate that the residue levels of pesticides in all tested honey did not pose a significant risk for human consumption. Out of all pesticides, aldrin is the only one that requires further risk assessment to determine its potential impact on honeybee colonies.
Creating a Public Service Announcement as a Teaching Strategy to Advocate for Populations at Risk due to Climate Change
Authors: Laverentz Delois M. , Young Elizabeth 
Published: December 2024

Abstract
The 2022 National League for Nursing Vision Statement, Climate Change and Health, identified gaps in nursing education regarding the issue of climate change and its impact on at-risk populations. Our innovative teaching strategy requires nursing students to use clinical judgment to synthesize ideas and communicate the health risks of climate change for population at risk in a brief video or public service announcement. This teaching strategy can prepare nursing students to advocate for population health.
Pericapsular Nerve Group (PENG) Block Versus Lumbar Erector Spinae Plane Block (ESPB) in Pediatric Hip Surgery: A Randomized, Double-Blinded, Controlled Trial
Authors: Reysner Malgorzata , Reysner Tomasz , Janusz Piotr , Kowalski Grzegorz , Shadi Milud , Daroszewski Przemysław , Wieczorowska-Tobis Katarzyna , Kotwicki Tomasz 
Published: December 2024

Background:
The effectiveness and safety of the pericapsular nerve group (PENG) block and lumbar erector spinae plane block (ESPB) in pediatric hip surgeries is limited mainly to case reports. This study assessed the efficacy of ultrasound-guided PENG block versus lumbar ESPB under spinal anesthesia.

Methods:
Ninety patients aged 2 to 7 years, ASA I-III scheduled for hip surgery were randomly assigned to 3 equal groups, each receiving the PENG block group (n=30), the ESPB group (n=30), or the control group (n=30). After the spinal anesthesia, the block was performed with 0.5 kg/mL of 0.2% ropivacaine. The primary outcome was the pain scores (FLACC) 48 hours after surgery. The secondary outcomes included postoperative FLACC pain scores, neutrophile-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and total opioid consumption.

Results:
The FLACC score was significantly lower in the lumbar ESPB and PENG groups compared with the control group (P<0.0001) at all time points. The NLR and PLR levels were substantially lower in the PENG and lumbar ESPB groups (P<0.0001) compared with the control group. The NLR and PLR levels were significantly lower in the PENG and lumbar ESPB groups compared with the control group (P<0.0001). The total opioid consumption was significantly lower in the PENG and lumbar ESPB groups compared with the control group (P<0.0001). Forty-three percent of children in the PENG group and 50% of children in the lumbar ESPB group did not require opioids postoperatively.

Conclusions:
The PENG block and the lumbar ESPB provide efficient postoperative analgesia in children undergoing hip surgery. The PENG block and lumbar ESPB lower cumulative opioid consumption and the stress response to surgery, expressed by NLR and PLR levels.

Level of evidence:
Level I.
Lhx2 specifically expressed in hepatic stellate cells promotes liver regeneration and inhibits liver fibrosis
Authors: Tao Jiawang , Wu Zichao , Liang Yanran , Wang Jiongliang , Tang Miaoxiu , Huang Sunan , Jiang Fan , Zhou Guangqi , Guo Lin , Yuan Shengxian , Li Yinxiong , Wang Jie 
Published: December 2024

Background and Aims:
Promoting liver regeneration while inhibiting fibrogenesis represented an attractive strategy for treating liver diseases, with hepatic stellate cells (HSCs) being crucial to both processes. This study aimed to identify specific targets in HSCs that simultaneously facilitated regeneration and suppressed fibrosis, and elucidated their molecular mechanisms.

Approach and Results:
Through comparing acute and chronic liver injury mouse models induced by CCl4 injections, we revealed that HSCs exhibited dual functionality, expressing pro-regenerative and pro-fibrogenic genes following injury. Analyzing RNA-seq data from primary HSCs of these models, along with publicly available single-cell RNA-seq data of HSCs, we identified transcription factor Lhx2, specifically expressed in HSCs, emerged as a potential regulator of the dual functions. Notably, Lhx2 showed significantly higher expression in HSCs from healthy liver tissue compared to fibrotic liver, in both mouse and human models. Lhx2 knockdown impaired liver function recovery and cellular proliferation after acute liver injury. Consistent changes were observed in mice with HSC-specific Lhx2 overexpression. Additionally, Lhx2 overexpression not only promoted hepatocyte proliferation but also exhibited an anti-fibrogenic function after chronic injury. Mechanistically, Lhx2 suppressed multiple functions of activated HSCs, including fibrogenesis, proliferation and migration, and up-regulated SMAD6 to block TGF-β signaling pathway. Moreover, Lhx2 was an upstream regulator of various pro-regenerative factors, especially HGF, which is crucial for liver regeneration.

Conclusions:
We demonstrated that Lhx2 had pro-regenerative and anti-fibrogenic functions, and elucidated its regulatory mechanism. The study provided a potential target with dual effects for treating liver diseases.