bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circadian Rhythm Mechanisms Underlying Convergent Adaptation of Unihemispheric Slow-Wave Sleep in Marine Mammals
Authors: Yin Daiqing , Yu Zhenpeng , Jiang Haojia , Chong Yujie , Zhong Cuijuan , Xu Shixia , Yang Guang 
Published: December 2024

Abstract
Marine mammals have evolved unihemispheric slow-wave sleep, a unique state during which one cerebral hemisphere sleeps while the other remains awake, to mitigate the fundamental conflict between sleep and wakefulness. However, the underlying mechanisms remain largely unclear. Here, we use a comparative phylogenetic approach to analyze genes associated with light-dependent circadian mechanisms, aiming to reconstruct the evolution of the circadian rhythm pathway in mammals and to identify adaptively changed components likely to have contributed to the development of unihemispheric slow-wave sleep. Specifically, among eight genes with shared signals of positive selection in two unihemispheric slow-wave sleep-specific lineages, seven genes showed direct evidence of affecting sleep and spontaneous movements. Both in vitro and in vivo experiments indicated that functional innovation in cetacean and non-phocid pinniped FBXL21, which was found to undergo positive selection, may be beneficial for decoupling sleep–wake patterns from daily rhythms to sustain continuous swimming. For cetaceans exhibiting only unihemispheric slow-wave sleep, we identified 73 genes as rapidly evolving and 92 genes containing unique amino acid substitutions. Functional assays showed that a cetacean-specific mutation (F411Y) in NFIL3 led to a decrease in repressor activity and protein stability. Furthermore, convergent amino acid replacements detected in genes related to Ca2+ signaling and CREB phosphorylation suggest their crucial role in unihemispheric slow-wave sleep adaptation. Overall, this study enhances our understanding of the evolutionary mechanisms underlying unihemispheric slow-wave sleep and provides a foundation for investigating how circadian rhythm changes contribute to variations in sleep and circadian behavior.
Interaction of N-methylmesoporphyrin IX with a hybrid left-/right-handed G-quadruplex motif from the promoter of the SLC2A1 gene
Authors: Seth Paul , Xing Eric , Hendrickson Andrew D , Li Kevin , Monsen Robert , Chaires Jonathan B , Neidle Stephen , Yatsunyk Liliya A 
Published: December 2024

Abstract
Left-handed G-quadruplexes (LHG4s) belong to a class of recently discovered noncanonical DNA structures under the larger umbrella of G-quadruplex DNAs (G4s). The biological relevance of these structures and their ability to be targeted with classical G4 ligands is underexplored. Here, we explore whether the putative LHG4 DNA sequence from the SLC2A1 oncogene promoter maintains its left-handed characteristics upon addition of nucleotides in the 5′- and 3′-direction from its genomic context. We also investigate whether this sequence interacts with a well-established G4 binder, N-methylmesoporphyrin IX (NMM). We employed biophysical and X-ray structural studies to address these questions. Our results indicate that the sequence d[G(TGG)3TGA(TGG)4] (termed here as SLC) adopts a two-subunit, four-tetrad hybrid left-/right-handed G4 (LH/RHG4) topology. Addition of 5′-G or 5′-GG abolishes the left-handed fold in one subunit, while the addition of 3′-C or 3′-CA maintains the original fold. X-ray crystal structure analyses show that SLC maintains the same hybrid LH/RHG4 fold in the solid state and that NMM stacks onto the right-handed subunit of SLC. NMM binds to SLC with a 1:1 stoichiometry and a moderate-to-tight binding constant of 15 μM−1. This work deepens our understanding of LHG4 structures and their binding with traditional G4 ligands.
The nature of grief: implications for the neurobiology of emotion
Authors: Ratcliffe Matthew , Velasco Pablo Fernandez 
Published: December 2024

Abstract
This paper explores the limitations of neurobiological approaches to human emotional experience, focusing on the case of grief. We propose that grief is neither an episodic emotion nor a longer-term mood but instead a heterogeneous, temporally extended process. A grief process can incorporate all manner of experiences, thoughts, and activities, most or all of which are not grief-specific. Furthermore, its course over time is shaped in various different ways by interpersonal, social, and cultural environments. This poses methodological challenges for any attempt to relate grief to the brain. Grief also illustrates wider limitations of approaches that conceive of emotions as brief episodes, abstracted from the dynamic, holistic, longer-term organization of human emotional life.
Week 96 Results of Bictegravir/Emtricitabine/Tenofovir Alafenamide for HIV Treatment in People With Substance Use Disorders
Authors: Havens Joshua P , Bares Sara H , Lyden Elizabeth , Fadul Nada , Swindells Susan 
Published: December 2024

Abstract

Background
The BASE study (NCT03998176), a phase 4, 48-week (W), single-arm, prospective trial, revealed that the use of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with HIV and substance use disorders (PWH/SUD) was safe and effective without emergent antiretroviral resistance despite incomplete adherence. Here, we present the W96 results.

Methods
A retrospective analysis of all participants enrolled in the BASE study was completed from W48 to W96. End points of interest at W96 included the proportion of participants with viral suppression (VS; HIV RNA &lt;50 copies/mL [c/mL]), incidence of protocol-defined virologic failure (PDVF; 2 consecutive ≥400 c/mL), safety, adherence (percentage of days covered [PDC]), retention in care, and prevalence of ongoing substance use.

Results
All enrolled BASE participants (n = 43) were included in the W96 analysis. At W48, 21 participants (49%) had achieved VS (intent-to-treat [ITT]). Thirty-six (84%) participants completed W96, with 19 achieving an HIV RNA &lt;50 copies/mL (ITT, 44%; per-protocol, 54%). Seven participants (19%) met PDVF; genotyping was performed on 2, with no evidence of treatment-emergent antiretroviral resistance noted. No safety signals were identified or attributed to B/F/TAF. Adherence to B/F/TAF decreased 18% after W48 (mean PDC: W0–W48, 72%; W48–W96, 54%; P &lt; .01). Participants exhibiting adherence rates of ≥4 doses/wk (PDC ≥57%) were more likely to achieve VS (PDC ≥57%, 84.2%, vs PDC &lt;57%, 15.8%; P &lt; .01). Retention in care remained stable, and participants continued to use substances through W96.

Conclusions
At W96, the proportion of PWH/SUD achieving VS with B/F/TAF decreased to 44%, along with an adherence decrease of 18%, with no evidence of treatment-emergent HIV drug resistance occurring.
The Economic Burden of Herpes Zoster in Individuals Aged 50 Years or Older and Those With Underlying Conditions in Italy
Authors: Zarkadoulas Eleftherios , Comparoni Simona , Freguja Riccardo , Santacroce Roberto , Dovizio Melania , Veronesi Chiara , Degli Esposti Luca , Gentile Ivan , Bonanni Paolo , Rossi Alessandro 
Published: December 2024

Abstract

Background
Risk of herpes zoster (HZ) infection increases with age and immunosuppression. We estimated the impact of HZ and post-herpetic neuralgia (PHN) on direct costs and health care resource utilization (HCRU) in patients ≥50 years, including those with comorbidities, as limited information exists in Italy.

Methods
This retrospective analysis used reimbursement data from local health authorities in Italy (January 2009–June 2022). Cases of HZ and PHN identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes and drug prescriptions were characterized and followed up for 1 year before and after the index date. The direct HCRU costs for patients with HZ/PHN were compared with those for patients without HZ/PHN.

Results
Of the total 193 259 patients with HZ/PHN identified (mean age, 61.6 years), 145 923 were ≥50 years old (immunocompromised: 29.9%; ≥1 chronic condition: 76.1%). During follow-up, 18.8% of patients ≥50 years of age with HZ progressed to PHN complications, and 3618 hospital admissions were reported (median length of stay, 9 days). Drug prescriptions and all-cause hospitalizations were the main contributors to total annual direct health care costs, estimated at M€272 for patients with HZ/PHN, whose burden increased with age. Higher health care costs were observed in patients with HZ/PHN vs patients without HZ/PHN. Moreover, average health care costs were up to 4× higher for patients with HZ and PHN compared with those without PHN.

Conclusions
HZ causes a significant economic impact on the health care system, driven mainly by high costs of medications and hospitalizations among older adults and those with comorbidities, particularly when complicated by PHN.
Weight loss in patients on osimertinib for metastatic EGFR-mutant non-small cell lung cancer
Authors: Chen Lanyi Nora , Ma Xin , Herzberg Benjamin , Henick Brian S , Biswas Anup K , Acharyya Swarnali , Shu Catherine A 
Published: December 2024

Abstract

Background
Cachexia is characterized by weight loss and decline in muscle mass and function and is a poor prognostic factor among patients with cancer. Patients with metastatic EGFR-mutant non-small cell lung cancer (NSCLC) derive remarkable survival benefits with osimertinib, a third-generation EGFR tyrosine kinase inhibitor. It is not known whether patients treated with osimertinib experience any weight loss or whether weight loss impacts patient outcomes. Therefore, we sought to describe the frequency and consequences of weight loss in this patient population.

Materials and methods
We conducted a single-center retrospective pilot study of 56 patients treated with first-line osimertinib for metastatic EGFR-mutant NSCLC. We defined on-treatment weight loss as a loss of ≥5% body weight at 6 or 12 months of treatment. We described the characteristics of patients with and without on-treatment weight loss and differences in progression-free survival (PFS), time on treatment with osimertinib, and overall survival (OS).

Results
Forty-six percent (n = 26) of patients met the criteria for on-treatment weight loss. There were no significant differences in patient or disease characteristics between patients with and without weight loss. Compared to patients without weight loss, patients with weight loss had similar PFS and time on treatment with osimertinib. Yet, patients with weight loss had significantly worse overall survival (HR 4.91, 95% CI, 1.56-15.5, P = .007).

Conclusion
Weight loss was observed in nearly half of patients with metastatic EGFR-mutant NSCLC treated with osimertinib, and patients with weight loss had significantly worse overall survival.
Macroevolution of body extremities reveals an integrated phenotypic response of coloration and morphology to temperature in a large clade of Neotropical passerines (Furnariida)
Authors: Macedo Gabriel , Marcondes Rafael S , Bravo Gustavo A , Derryberry Elizabeth P , Biondo Cibele 
Published: December 2024

ABSTRACT
Endotherms show smaller extremities (Allen’s rule) and larger body sizes (Bergmann’s rule) in colder climates, thereby reducing heat loss. Coloration can also be important in thermoregulation, as darker coloration absorbs more radiant energy than lighter coloration (Bogert’s rule or thermal melanism hypothesis). Extremities lacking or bearing thinner covers of feathers or fur—such as ears, legs and bills—can be important thermal windows to exchange heat. Yet, no study to date has simultaneously investigated the coloration and morphology of body extremities in relation to temperature. In 566 species of Furnariida (Neotropical ovenbirds and allies), we tested with phylogenetic comparative methods whether body extremity coloration, morphology and plumage coloration jointly respond to temperature. We predicted that, in colder climates, bills and tarsi would be darker and smaller as well as associated with darker plumage and larger body sizes. Consistent with this prediction, we found that bills are darker, smaller and are associated with darker plumage and larger body sizes in colder climates. Tarsi are darker and associated with darker plumage and larger body sizes in colder climates, but tarsus coloration is not associated with tarsus length, which, contrary to predictions of Allen’s rule, was longer in colder climates. Using phylogenetic path analyses, we found that climate affects body extremity coloration both directly and indirectly through its effects on habitat type, plumage coloration, and morphology. Our study suggests that temperature promotes an integrated phenotypic response of coloration and morphology across body extremities, plumage, and body size.
A review on recent progress in synthesis, properties, and applications of MXenes
Authors: Borah Ashish Jyoti , Natu Varun , Biswas Abhijit , Srivastava Anchal 
Published: December 2024

Abstract
MXenes, a noble class of two-dimensional (2D) material, discovered in 2011 have gained attention in recent years. They have attracted significant attention due to their flexible elemental composition, distinctive 2D-layered architecture, large surface area, and abundant surface terminations. Top-down synthesis techniques such as HF etching, alkaline etching, and electrochemical methods are used for MXene synthesis. Alongside these methods, methods like chemical vapor deposition (CVD), template method and plasma enhanced pulsed layer deposition (PELPD) are also used for the thin-film synthesis of MXenes. The discovery of double transition-metal layered MXene, solid, and high entropy MXene open up the prospect of further novel structures. MXenes are electrically conductive and have promising optoelectronic, mechanical, and thermoelectric properties. MXenes have also shown immense potential in biomedicine and environmental applications. The surface chemistry of MXene make them ideal for biosensors, drug delivery, and photothermal therapy, while their photocatalytic and adsorption properties enable efficient removal of pollutants and contaminants from water. This review examines the various MAX phase synthesis methods, such as solid-state reactions, hot isostatic pressing, and spark plasma sintering, followed by top-down techniques like HF etching, alkaline etching, and electrochemical etching, as well as bottom-up methods like CVD, template approaches, and plasma-enhanced pulsed layer deposition. The review also looks into the optical, chemical, and electronic properties of MXene, as well as their advancements in energy storage, optoelectronics, pollution avoidance, biomedical applications, and more.
Phase separation of MYB73 regulates seed oil biosynthesis in Arabidopsis
Authors: Yang Yuzhou , Kong Que , Ma Zhiming , Lim Peng Ken , Singh Sanjay K , Pattanaik Sitakanta , Mutwil Marek , Miao Yansong , Yuan Ling , Ma Wei 
Published: December 2024

Abstract
MYB family transcription factors (TFs) play crucial roles in plant development, metabolism, and responses to various stresses. However, whether MYB TFs are involved in regulating fatty acid biosynthesis in seeds remains largely elusive. Here, we demonstrated that transgenic Arabidopsis (Arabidopsis thaliana) plants overexpressing MYB73 exhibit altered FATTY ACID ELONGATION1 (FAE1) expression, seed oil content, and seed fatty acid composition. Electrophoretic mobility shift assays showed that FAE1 is a direct target of MYB73, and functional assays revealed that MYB73 represses FAE1 promoter activity. Transcriptomic analysis of the MYB73-overexpressing plants detected significant changes in the expression of genes involved in fatty acid biosynthesis and triacylglycerol assembly. Furthermore, MYB73 expression was responsive to abscisic acid (ABA), and ABA-responsive element binding factor 2 directly bound to the ABA-responsive element in the MYB73 promoter to activate its expression. Additionally, we determined that MYB73 exhibits the hallmarks of an intrinsically disordered protein and forms phase-separated condensates with liquid-like characteristics, which are important in regulating target gene expression. Together, our findings suggest that MYB73 condensate formation likely fine-tunes seed oil biosynthesis.
Productive infection of the retinal pigment epithelium by SARS-CoV-2: Initial effects and consideration of long-term consequences
Authors: Hultgren Nan W , Petcherski Anton , Torriano Simona , Komirisetty Ravikiran , Sharma Madhav , Zhou Tianli , Burgess Barry L , Ngo Jennifer , Osto Corey , Shabane Byourak , Shirihai Orian S , Kelesidis Theodoros , Williams David S 
Published: December 2024

Abstract
As the SARS-CoV-2 coronavirus continues to evolve and infect the global population, many individuals are likely to suffer from post-acute sequelae of SARS-CoV-2 infection (PASC). Manifestations of PASC include vision symptoms, but little is known about the ability of SARS-CoV-2 to infect and impact the retinal cells. Here, we demonstrate that SARS-CoV-2 can infect and perturb the retinal pigment epithelium (RPE) in vivo, after intranasal inoculation of a transgenic mouse model of SARS-CoV-2 infection, and in cell culture. Separate lentiviral studies showed that SARS-CoV-2 Spike protein mediates viral entry and replication in RPE cells, while the Envelope and ORF3a proteins induce morphological changes. Infection with major variants of SARS-CoV-2 compromised the RPE barrier function and phagocytic capacity. It also caused complement activation and production of cytokines and chemokines, resulting in an inflammatory response that spread across the RPE layer. This inflammatory signature has similarities to that associated with the onset of age-related macular degeneration (AMD), a major cause of human blindness, resulting from RPE pathology that eventually leads to photoreceptor cell loss. Thus, our findings suggest that post-acute sequelae of SARS-CoV-2 infection of the RPE may have long-term implications for vision, perhaps comparable to the increased occurrence of AMD found among individuals infected by HIV, but with greater public health consequences due to the much larger number of SARS-CoV-2 infections.
Improving debriefing practices for participants in social science experiments
Authors: Clayton Katherine , Porter Ethan , Velez Yamil , Wood Thomas J 
Published: December 2024

Abstract
Social science experiments often expose participants to false, deceptive, or otherwise harmful content. In an effort to mitigate the effects of such content and to comply with regulatory standards, these studies usually conclude by “debriefing” participants about the content they encountered, on the assumption that doing so will eliminate the effects of exposure. We present evidence showing that this assumption is not always correct. After standard debriefs, participants who have seen political misinformation often remain worse-informed than if they had never been exposed to misinformation in the first place. We then design and test a new approach to debriefing, which entails (i) debriefing as soon after exposure to harmful content as possible; (ii) providing an informative correction; and (iii) requiring participants to affirm that they have been exposed to false information. Across multiple experiments, we show that this approach is far superior to standard debriefs at reducing the effects of false or harmful content on political attitudes and beliefs. Our approach makes it possible to study the effects of false or harmful content on attitudes and beliefs without posing significant risks to participants.
ZHX3 interacts with CEBPB to repress hepatic gluconeogenic gene expression and uric acid secretion
Authors: Tan Wei Xuan , Lim Lillian Yuxian , Afsha Nesha , Chan Gloria Mei En , Ching Carmen , Oguz Gokce , Neo Suat Peng , Mohamed Ali Safiah , Ramasamy Adaikalavan , Gunaratne Jayantha , Hunziker Walter , Khoo Chin Meng , Teo Adrian Kee Keong 
Published: December 2024

Abstract
ZHX3, which encodes for a transcriptional repressor, is associated with fasting blood glucose (FBG) levels and increased type 2 diabetes (T2D) risk but its role in cell types involved in glucose metabolism is not well understood. Here, we show that the deletion of ZHX3 in the human pancreatic β-cell line EndoC-βH1 did not impair glucose-stimulated insulin secretion (GSIS) nor perturb its transcriptome. On the other hand, we found that ZHX3 represses the expression of gluconeogenic genes PCK1 and G6PC1 in the human hepatoma line HepG2. Transcriptomic analysis of ZHX3-deficient HepG2 cells revealed that the uric acid transporter gene SLC17A1 was up-regulated, which consequentially led to increased uric acid secretion. High levels of uric acid could then impair GSIS in EndoC-βH1 cells. Subsequently, in-depth co-immunoprecipitation followed by mass spectrometry analysis of ZHX3 in HepG2 cells identified transcription factor CEBPB as its binding partner, required to repress the transcription of PCK1, G6PC1, and partially SLC17A1 in HepG2 cells. Overall, our study uncovered the role of ZHX3 in regulating glucose metabolism in hepatocytes, thereby influencing FBG levels and their association with T2D risk.
The comparison of the efficacy of intramuscular tetracosactide and subacromial triamcinolone injection in rotator cuff tendinitis: a randomized trial
Authors: Orandi Amir Hossein , Mansour Amirpasha , Bagheri Nima , Majedi Hossein , Emami Meibodi Seyed Ali , Pestehei Seyed Khalil , Saberian Peyman 
Published: December 2024

Abstract

Objectives
Rotator cuff tendinitis (RCT) is a tendon inflammation often following subacromial impingement syndrome. One of the non-surgical management modalities for RCT is subacromial injection of corticosteroids. Some studies have claimed a correlation between ACTH (Adrenocorticotropic Hormone) deficiency and rotator cuff lesions; hence, intramuscular ACTH analogue injection has been recommended as an option. This research aimed to compare the effectiveness of these two treatment methods.

Methods
We conducted a study with 86 patients suffering from RCT. The patients were randomly divided into two groups of 43; one group received a subacromial injection of 40 mg of triamcinolone acetonide, while the other group received 1 mg of intramuscular tetracosactide injection. We recorded the Constant–Murley (CM) and visual analogue scale (VAS) scores for each patient before and 4 weeks after injections to measure pain acuity and joint functionality. Later, we compared and analysed the two scores in each group.

Results
Based on the statistical analysis, the mean ages of the participants in the triamcinolone and tetracosactide groups were 53.21 ± 11.37 and 54.56 ± 11.98, respectively. Both groups demonstrated an improvement in VAS for pain and CM scores (P &lt; 0.05). However, the VAS for pain score decreased, and the CM score increased more significantly in the triamcinolone group than in the tetracosactide group (P &lt; 0.05).

Conclusion
Although both treatment methods exhibit promise for pain relief, subacromial injection of triamcinolone appears more efficacious than intramuscular injection of tetracosactide in patients with RCT, based on a 4-week follow-up.

Trial registration
Iranian Registry of Clinical Trials, https://irct.behdasht.gov.ir, IRCT20240110060673N1.