bluuebunny/crossref_metadata_2025_split huggingface dataset:
Navigating triplet repeats sequencing: concepts, methodological challenges and perspective for Huntington’s disease
Authors: Maestri Simone , Scalzo Davide , Damaggio Gianluca , Zobel Martina , Besusso Dario , Cattaneo Elena 
Published: December 2024

Abstract
The accurate characterization of triplet repeats, especially the overrepresented CAG repeats, is increasingly relevant for several reasons. First, germline expansion of CAG repeats above a gene-specific threshold causes multiple neurodegenerative disorders; for instance, Huntington’s disease (HD) is triggered by &gt;36 CAG repeats in the huntingtin (HTT) gene. Second, extreme expansions up to 800 CAG repeats have been found in specific cell types affected by the disease. Third, synonymous single nucleotide variants within the CAG repeat stretch influence the age of disease onset. Thus, new sequencing-based protocols that profile both the length and the exact nucleotide sequence of triplet repeats are crucial. Various strategies to enrich the target gene over the background, along with sequencing platforms and bioinformatic pipelines, are under development. This review discusses the concepts, challenges, and methodological opportunities for analyzing triplet repeats, using HD as a case study. Starting with traditional approaches, we will explore how sequencing-based methods have evolved to meet increasing scientific demands. We will also highlight experimental and bioinformatic challenges, aiming to provide a guide for accurate triplet repeat characterization for diagnostic and therapeutic purposes.
Direct delivery of Cas-embedded cytosine base editors as ribonucleoprotein complexes for efficient and accurate editing of clinically relevant targets
Authors: Lee Jeong Min , Zeng Jing , Liu Pengpeng , Nguyen My Anh , Suchenski Loustaunau Diego , Bauer Daniel E , Kurt Yilmaz Nese , Wolfe Scot A , Schiffer Celia A 
Published: December 2024

Abstract
Recently, cytosine base editors (CBEs) have emerged as a promising therapeutic tool for specific editing of single nucleotide variants and disrupting specific genes associated with disease. Despite this promise, the currently available CBEs have the significant liabilities of off-target and bystander editing activities, partly due to the mechanism by which they are delivered, causing limitations in their potential applications. In this study, we engineered optimized, soluble and stable Cas-embedded CBEs (CE_CBEs) that integrate several recent advances, which were efficiently formulated for direct delivery into cells as ribonucleoprotein (RNP) complexes. Our resulting CE_CBE RNP complexes efficiently target cytosines in TC dinucleotides with minimal off-target or bystander mutations. Delivery of additional uracil glycosylase inhibitor protein in trans further increased C-to-T editing efficiency and target purity in a dose-dependent manner, minimizing indel formation. A single electroporation was sufficient to effectively edit the therapeutically relevant locus BCL11A for sickle cell disease in hematopoietic stem and progenitor cells in a dose-dependent manner without cellular toxicity. Significantly, these CE_CBE RNPs permitted highly efficient editing and engraftment of transplanted cells in mice. Thus, our designed CBE proteins provide promising reagents for RNP-based editing at disease-related sites.
Transforming girls’ education through social awareness and government interventions: a pathway to equality
Authors: Jha Rohan , Jha Rishabh , Islam Mazhar 
Published: December 2024

Abstract
This paper examines improvements in girls’ participation and performance in education in Bihar, India, focusing on the impacts of three government programs, namely, the Cycle Program, Cash Incentives and Syllabus Upgrades. We analyzed 20 years of standardized 10th-grade examination results alongside survey and interview data from students, teachers and parents. Our findings show that the Cycle Program and Cash Incentives significantly increased girls’ attendance and their likelihood of passing with a minimum acceptable passing score (third division) while having limited effects on boys. However, these interventions had a minimal impact on distinctive score (first division) for both genders. We also find that while girls still lag behind boys in academic performance, they are rapidly closing the gap due to these government interventions, greater access to resources and rising social awareness. For instance, gender disparities in participation and third-division results, particularly in rural districts, are shrinking. The survey of 507 participants and interviews indicate that societal changes, resource availability and increased parental support are playing critical roles in this shift. However, additional government initiatives—such as better teachers, curricula and incentives—are needed to further improve girls’ academic performance. These findings offer valuable insights for enhancing female school enrollment and education quality in Bihar and can serve as a model for other regions and countries facing similar educational challenges, including Chad, Niger, Liberia and Mali.
Freezing transition and moments of moments of the riemann zeta function
Authors: Curran Michael J 
Published: December 2024

ABSTRACT
Moments of moments of the Riemann zeta function, defined by $$ \text{MoM}_T(k,\beta) := \frac{1}{T}\int_T^{2T} \Bigg(\,\int\limits_{ |h|\leq (\log T)^\theta}|\zeta(\frac{1}{2} + i t + ih)|^{2\beta}\ dh\Bigg)^k\ dt, $$ where $k,\beta \geq 0$ and $\theta \gt -1$ were introduced by Fyodorov and Keating, Freezing transitions and extreme values: random matrix theory, and disordered landscapes, Philos. Trans. Roy. Soc. A: 372 no. 2007 (2014), 20120503 A doi:10.1098/rsta.2012.0503 when comparing extreme values of zeta in short intervals to those of characteristic polynomials of random unitary matrices. We study the k = 2 case as $T \rightarrow \infty$ and obtain sharp upper bounds for $\text{MoM}_T(2,\beta)$ for all real $0\leq \beta \leq 1$ as well as lower bounds of the conjectured order for all $\beta \geq 0$. In particular, we show that the second moment of moments undergoes a freezing phase transition with critical exponent $\beta = \frac{1}{\sqrt{2}}$. The main technical ingredient is a new estimate for the correlation of two shifted $2\beta^{\text{th}}$ powers of zeta with $0\leq \beta \leq 1$.
Radiation dose and image quality in pediatric bitewing imaging
Authors: Rajalingam Raheis , Brage Karen , Nielsen Louise Kjærby , Eriksen Freja Bøgh , Jørgensen Helene Hviid , Mikkelsen Anne Sofie , Schøler Gitte , Mekiš Nejc , Bruvo Maja , Precht Helle 
Published: December 2024

Abstract
Introduction: Bitewing examinations are used to examine the pediatric dental status. The aim of this study was to compare the image quality and radiation dose between two different X-ray systems used for pediatric bitewing imaging. Materials and Methods: Data were obtained from both pediatric in vivo bitewing studies and phantom studies. Two X-ray systems were used: Trophy CCX digital (TCCX) (Trophy Irix 70, Marne-la-Vallee, France) and Planmeca Pro X (PPX) (Planmeca, Helsinki, Finland). An Unfors dosimeter (Unfors EDD-30, Billdal, Sweden) was used to measure the skin dose. Image quality was evaluated blindly by three experienced dentists using a Likert scale of 1–5 based on the visual representation of the anatomical structures with emphasis on caries. Results: The highest scoring in vivo bitewing images were obtained with TCCX, but the skin dose was 36% higher (mean 3029 ± 613 μGy) and 113% higher (mean 1364 ± 276 μGy) with standard settings than with compared to PPX. The evaluation of image quality revealed a higher median value for all ratings of TCCX compared to PPX for both the patient and phantom studies, meaning that the images of TCCX were rated as higher quality than the images from PPX. No correlation was found between the median score and the skin dose or between the median score and the exposure times. Conclusion: A significant difference in radiation dose and image quality was found between TCCX and PPX in bitewing imaging. TCCX generally produced higher doses and better graded images, although all images were suitable for diagnosis.
New specimens of Saturnalia tupiniquim (Dinosauria: Sauropodomorpha): insights into intraspecific variation, rostral anatomy, and skull size
Authors: Damke Lísie V S , Langer Max C , Da-Rosa Átila A S , Müller Rodrigo T 
Published: December 2024

Abstract
Dinosaurs arose in the Late Triassic and diversified during the subsequent periods of the Mesozoic Era. The oldest unequivocal dinosaurs come from Carnian deposits of Brazil, Argentina, India, and Zimbabwe, with sauropodomorphs representing the bulk of this record. Saturnalia tupiniquim was described from Brazilian strata in 1999 as the first Carnian member of that group. Although several new species and specimens of coeval sauropodomorphs have been described in recent years, no new material has been formally assigned to that species. In this contribution, we describe an association of at least three partially preserved individuals of S. tupiniquim (UFSM 11660), which was excavated from the S. tupiniquim type-locality (Late Triassic of the Santa Maria Formation) and preserves cranial and postcranial elements, including the first rostrum known for the species. Assigned to S. tupiniquim according to several lines of evidence, the new specimen has a proportionally short rostrum, compared to that of coeval sauropodomorphs, providing evidence for a reduced skull in S. tupiniquim. In addition, we investigated the intraspecific variation in S. tupiniquim, highlighting the need to understand the morphological limits of such variations among the earliest dinosaurs, in order to properly explore their alpha diversity.
Immune aging and infectious diseases
Authors: Chen Ruochan , Zou Ju , Chen Jiawang , Wang Ling , Kang Rui , Tang Daolin 
Published: December 2024

Abstract
The rise in global life expectancy has led to an increase in the older population, presenting significant challenges in managing infectious diseases. Aging affects the innate and adaptive immune systems, resulting in chronic low-grade inflammation (inflammaging) and immune function decline (immunosenescence). These changes would impair defense mechanisms, increase susceptibility to infections and reduce vaccine efficacy in older adults. Cellular senescence exacerbates these issues by releasing pro-inflammatory factors, further perpetuating chronic inflammation. Moreover, comorbidities, such as cardiovascular disease and diabetes, which are common in older adults, amplify immune dysfunction, while immunosuppressive medications further complicate responses to infections. This review explores the molecular and cellular mechanisms driving inflammaging and immunosenescence, focusing on genomic instability, telomere attrition, and mitochondrial dysfunction. Additionally, we discussed how aging-associated immune alterations influence responses to bacterial, viral, and parasitic infections and evaluated emerging antiaging strategies, aimed at mitigating these effects to improve health outcomes in the aging population.
Navigating the complex role of senescence in liver disease
Authors: Li Qiuting , Wang Lin 
Published: December 2024

Abstract
Cellular senescence, an irreversible state of cell cycle arrest characterized by phenotypic changes and a specific secretory profile, plays a dual role in liver health and disease. Under physiological conditions, senescence aids organ repair and regeneration, but its accumulation due to aging or pathological stress significantly contributes to chronic liver diseases, including alcoholic liver disease, metabolic dysfunction-associated steatohepatitis, liver fibrosis, and hepatocellular carcinoma. Senescence is identified by a range of cellular and molecular changes, such as morphological alterations, expression of cell cycle inhibitors, senescence-associated β-galactosidase activity, and nuclear membrane changes. The onset of senescence in organ cells can affect the entire organism, primarily through the senescence-associated secretory phenotype, which has autocrine, paracrine, and endocrine effects on tissue microenvironments. The objective of this review is to offer a contemporary overview of the pathophysiological events involving hepatic senescent cells and to elucidate their role in the onset and progression of liver diseases, particularly through mechanisms like telomere shortening, genomic and mitochondrial DNA damage, and inflammation. Additionally, this review discusses the emerging senolytic therapies aimed at targeting senescent cells to delay or mitigate liver disease progression. The therapeutic potential of these interventions, alongside their safety and effectiveness, highlights the need for further research to refine these approaches and address unresolved problems in the field of hepatic cellular senescence.
Tumor-infiltrating regulatory T cell: A promising therapeutic target in tumor microenvironment
Authors: Huang Tianning , Li Fan , Wang Yiming , Gu Jian , Lu Ling 
Published: December 2024

Abstract
Regulatory T cell (Tregs) predominantly maintain the immune balance and prevent autoimmunity via their immunosuppressive functions. However, tumor-infiltrating Tregs (TI-Tregs) may mediate tumor immune tolerance in complex tumor microenvironments, resulting in poor prognosis. Distinguishing specific TI-Treg subpopulations from peripheral Tregs and intratumoral conventional T cells (Tconvs) has recently emerged as an important topic in antitumor therapy. In this review, we summarize novel therapeutic approaches targeting both the metabolic pathways and hallmarks of TI-Tregs in preclinical and clinical studies. Although the phenotypic and functional diversity of TI-Tregs remains unclear, our review provides new insights into TI-Treg-based therapies and facilitates precision medicine for tumor treatment.
Clinical Symptoms of Postburn Hypertrophic Scars and Analysis of Risk Factors for Itching and Pain Requiring Pharmacological Intervention
Authors: Chen Bo , Jia Qing , Huang Jing , Gu YaoHui 
Published: December 2024

BACKGROUND
Pruritus and pain symptoms secondary to hypertrophic scars (HTSs) are associated with multiple factors, with age, body mass index (BMI), and scar thickness being the main risk factors (RFs).

OBJECTIVE
This study mainly discusses the clinical symptoms associated with postburn HTSs and analyzes RFs for itching and pain requiring pharmacological intervention.

MATERIALS AND METHODS
All clinical data of 93 patients with postburn HTSs who visited the Burn Department of Shanghai Seventh People's Hospital between January 1, 2021 and January 1, 2023 were collected and analyzed retrospectively. Referring to the University of North Carolina “4P” Scar Scale, patients were rated as either “with” or “without” according to whether they had “scar itching symptoms requiring pharmacological intervention.”

RESULTS
Smoking, third-degree burns, unused silicone drugs, and total burn surface area 30% to 50% were independent RFs for requiring pharmacological intervention for postburn scar pruritus (odds ratio [OR] = 2.998, 3.924, 3.588, and 5.965, p < .05). Age, increased BMI, greater scar thickness, and duration of hyperplasia not more than 1 year significantly increased the risk of scar pain requiring medical intervention (OR = 1.626, 2.441, 20.830, 11.646, and 11.136, p < .05).

CONCLUSION
The clinical value of these factors is that they can help physicians better identify those patients who may require pharmacological intervention to control itching and pain.
Femtosecond Laser- Assisted Customized CAIRS In Keratoconus Patients After ICRS Explantation: A Prospective Case Series
Authors: Susanna Bianca N , ForsetoMD Adriana S , SilveiraMD Aline M , Santhiago Marcony R , Susanna Fernanda N , Pereira Nicolas C 
Published: December 2024

Purpose:
To investigate the effectiveness and safety of customized femtosecond laser-assisted corneal allogenic intrastromal ring segments (CAIRS) implantation in keratoconus patients with a history of intrastromal corneal ring segment (ICRS) explantation.

Setting:
Sorocaba Eye Hospital (Hospital Oftalmológico de Sorocaba - HOS), Sorocaba, Brazil.

Design:
Prospective case series.

Methods:
We included eight keratoconus patients with stable disease and with history of ICRS explantation at least six months before the inclusion in the study. Patients were excluded if presenting any other ocular pathology. Customized CAIRS was produced and implanted using femtosecond laser LDV Z8 (Ziemer Ophthalmic Systems AG, Port, Switzerland). Patients were followed-up for six months.

Results:
The mean reduction of the maximum, mean, and steep central keratometry was 3.03 ± 1.35 diopters (D) (p =0.01), 2.88 ± 2.51 D (p=0.02), and 2.41 ± 2.72 D (p=0.04), respectively. The mean spherical equivalent and refractive astigmatism reduced 6.28 ± 2.71 D (p =0.01), and 1.62 ± 2.83 D (p=0.16). All eyes, but one gained two or more lines of best spectacle corrected visual acuity (BSCVA).
Additionally, five patients achieved a BSCVA of 20/40 or better. No intra or post-operative complications were observed.

Conclusions:
Customized femtosecond laser assisted CAIRS may be an effective and safe option for visual rehabilitation in keratoconus patients with previous ICRS explantation.
Posterior-superior insula repetitive transcranial magnetic stimulation reduces experimental tonic pain and pain-related cortical inhibition in humans
Authors: Chowdhury Nahian S. , Millard Samantha K. , de Martino Enrico , Larsen Dennis Boye , Seminowicz David A. , Schabrun Siobhan M. , de Andrade Daniel Ciampi , Graven-Nielsen Thomas 
Published: December 2024

Abstract
High frequency repetitive transcranial magnetic stimulation (rTMS) to the posterior-superior insula (PSI) may produce analgesic effects. However, the alterations in cortical activity during PSI-rTMS analgesia remain poorly understood. The present study aimed to determine whether tonic capsaicin-induced pain and cortical inhibition (indexed using TMS-electroencephalography) are modulated by PSI-rTMS. Twenty healthy volunteers (10 females) attended 2 sessions randomized to active or sham rTMS. Experimental pain was induced by capsaicin administered to the forearm for 90 minutes, with pain ratings collected every 5 minutes. Left PSI-rTMS was delivered (10 Hz, 100 pulses per train, 15 trains) ∼50 minutes postcapsaicin administration. Transcranial magnetic stimulation–evoked potentials (TEPs) and thermal sensitivity were assessed at baseline, during capsaicin pain prior to rTMS and after rTMS. Bayesian evidence of reduced pain scores and increased heat pain thresholds were found after active rTMS, with no changes occurring after sham rTMS. Pain (prior to active rTMS) led to an increase in the frontal negative peak ∼45 ms (N45) TEP relative to baseline. After active rTMS, there was a decrease in the N45 peak back to baseline levels. In contrast, after sham rTMS, the N45 peak was increased relative to baseline. We also found that the reduction in pain numerical rating scale scores after active vs sham rTMS was correlated with and partially mediated by decreases in the N45 peak. These findings provide evidence of the analgesic effects of PSI-rTMS and suggest that the TEP N45 peak is a potential marker and mediator of both pain and analgesia. This study demonstrates that high-frequency rTMS targeting the posterior-superior insula reduces capsaicin-induced pain and alters cortical activity, with changes in the N45 TMS-evoked potential peak mediating the analgesic effects.
A Comprehensive Unit-Based Safety Program to Enhance the Safe Management of Children in an Epilepsy Monitoring Unit
Authors: Wang Haiqin , Gan Hui , Zhou Qin , Dai Li 
Published: December 2024

ABSTRACT

BACKGROUND: The epilepsy monitoring unit (EMU) is an independent unit for video electroencephalogram monitoring of epilepsy patients, with the aim of capturing typical seizure events. Because of the uncontrolled seizure frequency, there may be safety risks for patients, such as falling, trauma, aspiration, status epilepticus, and sudden unexpected death in epilepsy. This study aims to evaluate the application effect of comprehensive safety projects on safety management in a pediatric EMU. METHODS: From June 2022 to May 2024, a preevaluation and postevaluation study was conducted at the EMU of a tertiary grade A children's specialized hospital in China. The intervention group carried out a unit-based comprehensive safety project, including nurse safety culture training, establishing a normalized mechanism for safety improvement, and developing evidence-based safety prevention strategies. RESULTS: The response time of paroxysmal events in the intervention group was shorter than that in the control group (P < .05). The scores of implementation of safety precautions and emergency measures in the intervention group were higher than those in the control group (P < .05). The nursing-related complications in the intervention group were lower than those in the control group (P < .05). CONCLUSION: The comprehensive unit-based safety project management mode can effectively improve the quality of EMU nursing care for children and reduce nursing-related complications.
Association of DNA methylation of RASSF1A and SHOX2 with lung cancer risk: A systematic review and meta-analysis
Authors: Guo Yixin , Wu Peiyi , Liao Qiwei , Huang Zhuo 
Published: December 2024

Background:
This study estimates the research upon the potential worth of Ras association domain family member 1 A (RASSF1A) and short stature homeobox 2 (SHOX2) DNA methylation in lung cancer (LC) diagnosis.

Methods:
Open-published research was searched through PubMed, EMBASE, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, and Chinese Biology Medicine Literature Database. Data on true positives, false positives, false negatives, and true negatives were extracted.

Results:
This meta-analysis included 22 studies encompassing 4109 subjects (2427 LC patients and 1682 controls). The combined sensitivity, specificity, and area under the curve for RASSF1A and SHOX2 DNA methylation were 0.77 (95% CI: 0.71–0.81), 0.90 (95% CI: 0.87–0.92), and 0.92 (95% CI: 0.87–0.92), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 7.5 (5.9–9.7) and 0.26 (0.21–0.32). The combined diagnostic odds ratio was 29 (95% CI: 20–41).

Conclusion:
RASSF1A and SHOX2 DNA methylation may emerge as potential diagnostic biomarkers for early-stage LC.