bluuebunny/crossref_metadata_2025 huggingface dataset:
Hibecovirus (genus Betacoronavirus) infection linked to gut microbial dysbiosis in bats
Authors: Melville Dominik W , Meyer Magdalena , Risely Alice , Wilhelm Kerstin , Baldwin Heather J , Badu Ebenezer K , Nkrumah Evans Ewald , Oppong Samuel Kingsley , Schwensow Nina , Tschapka Marco , Vallo Peter , Corman Victor M , Drosten Christian , Sommer Simone
Published: December 2024

Little is known about how zoonotic virus infections manifest in wildlife reservoirs. However, a common health consequence of enteric virus infections is gastrointestinal diseases following a shift in gut microbial composition. The sub-Saharan hipposiderid bat complex has recently emerged to host at least three coronaviruses (CoVs), with Hipposideros caffer D appearing particularly susceptible to Hibecovirus CoV-2B infection. In this study, we complement body condition and infection status data with information about the gut microbial community to understand the health impact of CoV infections in a wild bat population. Of the three CoVs, only infections with the distantly SARS-related Hibecovirus CoV-2B were associated with lower body condition and altered the gut microbial diversity and composition. The gut microbial community of infected bats became progressively less diverse and more dissimilar with infection intensity, arguing for dysbiosis as per the Anna-Karenina principle. Putatively beneficial bacteria, such as from the genera Alistipes and Christensenella, decreased with infection intensity, while potentially pathogenic bacteria, namely Mycoplasma and Staphylococcus, increased. Infections with enterically replicating viruses may therefore cause changes in body condition and gut dysbiosis with potential negative health consequences even in virus reservoirs. We argue that high-resolution data on multiple health markers, ideally including microbiome information, will provide a more nuanced picture of bat disease ecology.
Melatonin supplementation to sows in mid to late gestation affects offspring circadian, myogenic, and growth factor transcript abundance in pre and postnatal skeletal muscle
Authors: Dobbins Thomas W , Swanson Rebecca M , Dennis Amberly A , Rivera J Daniel , Dinh Thu T N , Lemley Caleb O , Burnett Derris D
Published: December 2024

The neuroendocrine hormone melatonin is associated with circadian rhythms and has antioxidant and vasodilative properties. In cattle, melatonin rescues fetal growth during maternal nutrient restriction in a seasonally dependent manner, but melatonin research in swine is limited. The objective of this study was to evaluate the effects of dietary melatonin supplementation during mid to late gestation on circadian rhythm and muscle growth and development of the longissimus dorsi in utero and postnatally. Sows received 20 mg of dietary melatonin daily (MEL) or no melatonin supplement (CON). Experiment 1 supplemented sows from gestational age (dGA) 38 ± 1 to 99 ± 1, experiment 2 supplemented sows from 41 to 106 ± 1 dGA, and experiment 3 supplemented sows from 60 dGA to farrowing. At harvest, morphometric measurements of all fetuses were taken, while the small (SM), medium (MED), and large (LG) piglets from each litter were used for further analysis. Prenatal data were analyzed using the MIXED procedure of SAS, and postnatal data were analyzed using the GLIMMIX procedure. Fetal morphometrics were analyzed for fixed the effect of treatment, and transcript abundance was analyzed for treatment, time, and size. Postnatal parameters were analyzed for fixed effects of treatment, size, and production stage. In experiment 1, MEL increased (P = 0.016) Period 1 (PER1) transcript abundance in the evening (PM) compared to the morning (AM). In experiment 1, myogenin (MYOG) transcript abundance was increased (P = 0.033) in MEL fetuses in the AM compared to MEL in the PM. Myogenic factor 5 (MYF5) and paired box 7 (PAX7) were increased (P = 0.016) in the PM. Fetuses from MEL-treated sows had increased (P < 0.05) BW, curve crown-rump length, and head circumference in experiment 2. In experiment 2, MEL increased (P = 0.012) PER1 and Period 2 (PER2) transcript abundance in the PM. In experiment 2, myoblast differentiation 1 (MYOD) was increased (P = 0.016) in SM and MED fetuses, while MYF5 and PAX7 were increased (P = 0.019) in SM fetuses. Postnatal BW was increased (P = 0.025) in MED and LG MEL-treated offspring compared to CON. Insulin-like growth factor 1 (IGF1) was downregulated (P = 0.050) in MEL-treated offspring, while insulin-like growth factor 1 receptor (IGF1R) was upregulated (P = 0.009) in MEL offspring. These results indicate that maternal melatonin supplementation during gestation modulates fetal circadian regulatory genes and alters myogenic genes during growth.
Species-specific differences in acetaminophen hepatotoxicity depend on HSP70 expression level
Authors: Tsuji Daisuke , Akagi Reiko
Published: December 2024

Acetaminophen (N-Acetyl-p-aminophenol: APAP) is one of the most commonly used analgesic/antipyretic drugs with proven safety at therapeutic doses, however, over-dosage causes dose-dependent liver damage, leading to acute liver failure in severe cases. The level of APAP-induced liver injury has been known to vary amongst animal species, and APAP concentrations that induce cell death have been investigated using primary cultured cells. We constructed in vitro model of APAP-induced hepatotoxicity using mouse, rat and human hepatoma cell lines to investigate species differences in the APAP-induced cytotoxicity by monitoring cell death as a marker. The EC50 for each cell line was Hepa1–6 (mouse) < H-4-II-E (rat) < Hep3B (human), whilst the expression of heat shock protein 70 (HSP70), which was a typical molecular chaperone, positively correlated with the EC50 of each cell. Heat shock treatment, which caused activation of heat shock factor 1 (HSF1) followed by significant induction of HSP70, partially suppressed APAP-induced cell death in Hepa1–6 and H-4-II-E. Moreover, HSP70 or HSF1 siRNA treatment in Hep3B enhanced APAP-induced cell death. These results suggest that APAP-induced cell death in hepatoma cell lines may be partly mediated by protein denaturation and that the expression level of HSP70 has an inhibitory effect.
The relationship between baseline bone mineral density and fracture incidence in the placebo groups of randomized controlled trials using individual patient data from the FNIH-ASBMR-SABRE project
Authors: Schini Marian , Lui Li-Yung , Vilaca Tatiane , Ewing Susan K , Thompson Austin , Bauer Douglas C , Bouxsein Mary L , Black Dennis M , Eastell Richard
Published: December 2024

We have proposed to the Food and Drug Administration (FDA) that treatment-related increases in total hip BMD (TH BMD) at 2 yr could be a surrogate endpoint for fracture risk reduction in clinical trials. The qualification of a surrogate includes a strong association of the surrogate with the clinical outcome. We compiled a large database of individual patient data (IPD) through the Foundation for the National Institutes of Health-American Society for Bone and Mineral Research- A Study to Advance BMD as a Regulatory Endpoint (FNIH-ASBMR-SABRE) project, and this analysis aimed to assess the relationship between baseline BMD and fracture risk in the placebo groups. We estimated the association of baseline TH, femoral neck (FN), and lumbar spine (LS) BMD with fracture risk using IPD from the combined placebo groups, which included data from 46 666 placebo participants in 25 RCTs. We estimated the relative risk (RR) of fracture per SD decrease in baseline BMD using logistic regression models for radiographic vertebral fractures and proportional hazards models for hip, non-vertebral, “all,” and “all clinical” fractures. Total person-years in the combined placebo groups was 250 662 (mean baseline age 70.2 ± 7.2 yr, mean TH BMD T-score −1.97 ± 0.90). We observed significant relationships between baseline TH BMD and vertebral (RR = 1.55/SD), hip (RR = 2.27), non-vertebral (RR = 1.31), all (RR = 1.43), and all clinical (RR = 1.35) fracture risk. Fracture risk estimates were similar for FN BMD and after adjustment for age, race, and study. Fracture incidence increased with decreasing TH BMD quintile, confirming the strong graded association between TH BMD and fracture risk. There was a strong relationship between LS BMD and vertebral fracture risk (RR = 1.56/SD), but only a weak association with non-vertebral (RR = 1.07) and no association with hip (RR = 1.01) fracture risk. These data support the very strong relationship between hip BMD and fracture risk and provide supporting rationale for change in TH BMD as a surrogate for fracture risk reduction in future RCTs.
Chromosome-level genome assembly of the king horseshoe bat (Rhinolophus rex) provides insights into its conservation status and chromosomal evolution of Rhinolophus
Authors: Lan Linjing , Zhang Xin , Yang Shanxiu , Mao Xiuguang , Dong Ji
Published: December 2024

A high-quality reference genome is quite valuable in assessing the conservation status of a rare species when adequate data from other sources are unavailable. Bats comprise almost a fifth of all mammals and contribute greatly to the ecosystem. However, due to the nocturnal and elusive habits, it is difficult to obtain the accurate census population size of a rare bat species and assess its conservation status. Here, we generate a chromosome-level genome assembly for the king horseshoe bat (Rhinolophus rex) and assess its conservation status by comparing the genome-wide summary statistics with other related species. The genome assembly size was 2.1 Gb (contig N50: 75.26 Mb) and 99.9% of the total sequences were anchored onto 30 autosomes, X and Y chromosomes. Despite lower genome-wide heterozygosity and recent inbreeding, R. rex did not exhibit a higher genetic load compared with the other two Rhinolophus species. Historical demography analysis revealed that R. rex maintained a long-term (~2 million years) stable population size (~150,000). In the future, whole-genome sequencing data from more individuals will be needed to comprehensively assess the conservation status at recent timescales. We also reconstructed the ancestral karyotype of Rhinolophus as 2n = 54 and found that Robertsonian fissions and fusions were the main mechanisms of chromosomal rearrangements in this genus. Overall, our study shows important implications of reference-quality genomes in both conservation genomics and comparative genomics.
Chronic occupational paronychia secondary to digital pilonidal sinus from dog grooming
Authors: Räisänen Mikko P , Furu Heidi , Reito Aleksi , Bindra Randy R
Published: December 2024

Pilonidal sinus is a recognized occupational condition sometimes seen in barbers and pet groomers, and it involves most commonly interdigital spaces. We present a previously unreported case of chronic paronychia with 2 separate digital pilonidal sinuses resulting from multiple embedded hair fragments in the eponychium of a dog groomer, who had been repeatedly treated with antibiotics with no success and ended up having surgical treatment. The objective of this study is to remind readers of this rare but possible occupational disease, particularly among employees working with hair, and to emphasize the importance of preventive measures to prevent its occurrence. Intraoperatively, a crescent of eponychial skin parallel to the proximal nail fold was excised, which incorporated the sinuses. Additionally, the nail plate was removed, and multiple hair fragments were retrieved from the nail folds. At the follow-up, the infection had resolved, and nail growth had resumed. Additional animal hair was found in the nail folds, as the patient continued to work without protective gloves. This case highlights the importance of considering embedded hair as a potential cause for chronic paronychia in individuals with occupations involving hair cutting and grooming. Chronic hand infection poses a risk of infection contaminating clients or patients; for example, a veterinarian should not operate with an infected hand. The costs of sickness absences are considerable for all the stakeholders. The use of protective gloves, hand hygiene, skin care, and thorough removal of loose hair fragments should be emphasized for workers in professions dealing with animal or human hair.
Cell-based and extracellular vesicle-based MSC therapies for acute radiation syndrome affecting organ systems
Authors: Miura Yasuo , Fujii Sumie , Ichinohe Tatsuo
Published: December 2024

Exposure to ionizing radiation can induce harmful biological effects on the human body, particularly in cases of high-dose γ-irradiation affecting the gastrointestinal tract, bone marrow, skin and lung. Such exposures lead to lethal outcomes as individuals experience a breakdown in their immune system’s ability to defend against pathogens, predisposing them to sepsis-induced multiple organ failures. Mesenchymal stromal/stem cells (MSCs) possess diverse biological characteristics, including immunomodulation, anti-inflammation and tissue regeneration. Off-the-shelf culture-expanded human bone marrow- or adipose tissue-derived MSCs are clinically available to treat graft-versus-host disease following hematopoietic cell transplantation and perianal fistulas in Crohn’s disease in Japan. While preclinical studies showcase encouraging outcomes in radiation-induced injuries, the effectiveness of MSC transplantation in addressing acute radiation syndrome affecting organs in irradiated individuals is limited. Recent studies have highlighted MSC-releasing extracellular vesicles as nanoparticle substances responsible for outlining the mechanism of action and have identified various components, including proteins and microRNA, that serve as functional molecules. MSC-releasing extracellular vesicle-based therapy emerges as a promising avenue, offering a potential solution to the challenges posed by radiation-induced injuries. However, further investigation is required, especially regarding whether MSC-releasing extracellular vesicles have regenerative effects on tissue-resident stem cells. These unresolved issues represent key aspects that need to be addressed to optimize the therapeutic potential of cell-based and extracellular vesicle-based MSC therapies for interventions in the context of radiation-induced injuries.
The summary of risk response on radioactive substances contained in food items in the aftermath of the Fukushima nuclear accident
Authors: Hayashida Naomi , Horiguchi Itsuko
Published: December 2024

The Fukushima Daiichi nuclear power plant accident occurred after the Great East Japan Earthquake on 11 March 2011. The regulations for food items contaminated with radioiodine or radioactive cesium were introduced immediately after the accident by establishing a tentative limit for the contamination level. These regulations excluded or minimized the excessive internal radiation exposure in Japan. Subsequently, the Food Safety Commission of the Japanese Cabinet Office established based on the Food Safety Basic Act evaluated the influence of food items on human health, and the information was reviewed to establish finalized reference values according to the Food Sanitation Act. This study aimed to compile a summary from published sources to examine the risk analysis conducted by the Japanese government over 5 years since the disaster occurred, which was carried out to prevent internal exposure to radioactive substances in food. Findings revealed that items exceeding the reference value were mostly found in the item group not under cultivation/feeding management. In addition, the risk management measures to prevent internal exposure to radioactive substances in food have proven to be effective.
Motherhood on the move: forced migrant women from Ukraine
Authors: Rock Jonna , Yanaşmayan Zeynep
Published: December 2024

Drawing on the experiences of thirty-two refugee mothers who fled Ukraine with their children to Germany—to Berlin and Frankfurt/Oder—this article traces the co-constitutive relationship of displacement and motherhood through the angle of temporality. First, it uncovers how displacement in motherhood is defined by mothers’ urge and urgency to protect their children. Second, it shows how refugee mothers utilize different forms of ‘active waiting’ to rebuild their lives in search of stability for themselves and their children and affectively deal with the trauma of multiple losses. Last but not least, motherhood in displacement generates new forms of maternal subjectivity as the interlocutors ‘spend their time’ to patch the ruptures in their lives for the sake of their children, not only alone but also together with other refugee mothers through digital means. Negotiating motherhood thus provides room to productively navigate a temporal disorientation caused by the displacement.
Associations between sexual activity frequency and depression in women: insights from the NHANES data
Authors: Wu Xu , Gao Hui , Zhang Yuyang , Zhang Xiansheng
Published: December 2024

Background

Existing research is very limited in providing nationally representative data on the relationship between sexual activity and depression in U.S. female adults aged 20–59 years, particularly with regard to marital status differences.

Objectives

Our specific objective was to explore the relationship between sexual activity and depression in adult women in the United States.

Methods

We conducted a study utilizing depression and sexuality data from the U.S. National Health and Nutrition Examination Survey (NHANES) for women aged 20-59 years between 2007 and 2016. Subsequently, we used survey-weighted logistic regression models to examine the relationship between low-frequency sexual activity and the risk of depression. To further explore the effects of different stratification factors on the relationship between low-frequency sexual activity and depression, we conducted subgroup analyses based on age, race, marital status, poverty-to-income ratio (PIR), education level, BMI, hypertension, diabetes mellitus, smoking, trouble sleeping, and urine Leakage. In addition, sensitivity analysis and smoothed curve fitting were performed to ensure the reliability of the results.

Main Outcome Measure

Sexual activity was assessed by sexual frequency, ≤11 sexual encounters in a 12-month period were categorized as low-frequency sexual activity; depression was diagnosed by the Patient Health Questionnaire (PHQ-9, ≥10 scores).

Results

From the 2007 to 2016 NHANES, a total of 6061 participants were enrolled in the study. Of these participants, 1869 (30.84%) reported a sexual frequency of 0-11 times/year categorized as low-frequency sexual activity. After adjustment for the full covariates, the risk of depression was found to be higher in low-frequency sexual activity participants (sexual frequency ≤ 11) compared to normal-frequency sexual activity participants (sexual frequency > 11) (OR = 1.37, 95 % CI: 1.08, 1.73; P = 0.010), this association varied according to marital status.

Clinical Implications

Our findings have important clinical implications and suggest that clinicians should pay attention to the mental health of female patients with low-frequency sexual activity and screen depressed patients for sexual activity.

Strengths & Limitations

Our study is the large, nationally representative study to assess the relationship between low-frequency sexual activity and depression in women aged 20 to 59 years. However, the cross-sectional study design was unable to demonstrate a causal relationship between low-frequency sexual activity and depression.

Conclusion

In conclusion, our study demonstrates a significant association between low frequency of sexual activity and risk of depression in a population of women aged 20 -59 years in the U.S, which may be bidirectional.
Mapping the risk of tick-borne encephalitis in Europe for informed vaccination decisions
Authors: Beerlage-de Jong Nienke , Blanford Justine
Published: December 2024

Tick-borne encephalitis is increasing across Europe, yet public awareness lags. Geo-visualizations leveraging openly available data empower travellers and health authorities in making informed (vaccination) choices. We urge improved surveillance and synchronization of data for easily accessible and understandable (geo) health information, to enhance early detection of infections.
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

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 >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

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

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

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

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

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.
N-Acetylcysteine in Agriculture: New Insights into Its Effects for Sustainable Crop Management
Authors: dos Santos Lucas N. , Cavalcante Lídia do N. , Rocha Dhiôvanna C. , Prado Guilherme S. , Coletta-Filho Helvecio D. , de Souza Alessandra A.
Published: December 2024

N-Acetylcysteine (NAC), an amino acid naturally found in Allium plants, is well-known for its health benefits in humans. However, its potential applications in plant health remain underexplored, especially considering that while thousands of studies are published annually in clinical research, fewer than 10 focus on its use in plants each year. This review consolidates recent findings on the role of NAC as a potent antioxidant molecule in mitigating both biotic and abiotic stresses in plants, highlighting its valuable contributions to sustainable agriculture. NAC reduces oxidative stress by directly scavenging reactive oxygen species (ROS) and indirectly increasing cysteine and glutathione levels, both critical for cellular defense responses. Moreover, NAC breaks intramolecular and intermolecular disulfide bonds in thiolated proteins, potentially further enhancing its antioxidant effects by releasing free thiols. It also functions as a chelating agent, binding to heavy metals and reducing their toxicity. Furthermore, NAC’s efficacy in controlling bacterial infections in humans and animals—through mechanisms such as disrupting disulfide bonds in extracellular proteins and breaking down biofilm matrices—has been shown to extend to plant pathosystems, where it aids in suppressing bacterial pathogens. In addition to stress alleviation, NAC has been demonstrated to enhance crop productivity, improve food quality, and offer ecological benefits by promoting the health of pollinators and free-living soil organisms. These multifaceted attributes highlight NAC’s potential as a key tool in agriculture, helping to improve plant resilience, support ecosystem balance, and advance sustainable crop management practices.
Immune aging and infectious diseases
Authors: Chen Ruochan , Zou Ju , Chen Jiawang , Wang Ling , Kang Rui , Tang Daolin
Published: December 2024

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

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

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

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

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.
Clinical Practice With Preprimed Extracorporeal Membrane Oxygenation: Safety, Sterility, and Functionality
Authors: Renghini Mauro , Maddinelli Debora , Papeo Anna , Puglia Carmine , Montisci Andrea , Cattaneo Sergio , Benussi Stefano
Published: December 2024

This 5 year retrospective study presents the clinical experience with preprimed extracorporeal membrane oxygenation (ECMO) circuits used in a Single Hub Center Hospital, focusing on sterility, functionality, and safety. The ECMO program has been active since 2019, with a total of 223 circuits managed. Our preassembled and preprimed ECMO circuits were stored in a sterile environment and continuously circulated until implantation. Sterility and functionality testing was performed at the end of circuit preparation, every 7 days, and before implantation. Our results show that only 2 (0.3%) of the 570 samples tested positive for bacteria, and all implanted devices demonstrated satisfactory gas transfer performance. None of the ECMO devices demonstrated any loss of early functionality after implantation. The longest storage period of a preprimed circuit was 73 days, with no positive culture results. Our study highlights the importance of preassembled and preprimed ECMO circuits in improving clinical practice in emergency situations, highlighting their safety and potential to improve clinical practice. Furthermore, our findings suggest that standardizing guidelines for prepriming and storage of ECMO circuits can help minimize the risk of contamination.
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.