bluuebunny/crossref_metadata_2025 huggingface dataset:
CETP and SGLT2 inhibitor combination therapy increases glycemic control: a 2x2 factorial Mendelian randomization analysis
Authors: Khomtchouk Bohdan B. , Sun Patrick , Maggio Zane A. , Ditmarsch Marc , Kastelein John J. P. , Davidson Michael H.
Published: June 2024

Introduction

Cholesteryl ester transfer protein (CETP) inhibitors, initially developed for treating hyperlipidemia, have shown promise in reducing the risk of new-onset diabetes during clinical trials. This positions CETP inhibitors as potential candidates for repurposing in metabolic disease treatment. Given their oral administration, they could complement existing oral medications like sodium-glucose cotransporter 2 (SGLT2) inhibitors, potentially delaying the need for injectable therapies such as insulin.

Methods

We conducted a 2x2 factorial Mendelian Randomization analysis involving 233,765 participants from the UK Biobank. This study aimed to evaluate whether simultaneous genetic inhibition of CETP and SGLT2 enhances glycemic control compared to inhibiting each separately.

Results

Our findings indicate that dual genetic inhibition of CETP and SGLT2 significantly reduces glycated hemoglobin levels compared to controls and single-agent inhibition. Additionally, the combined inhibition is linked to a lower incidence of diabetes compared to both the control group and SGLT2 inhibition alone.

Discussion

These results suggest that combining CETP and SGLT2 inhibitor therapies may offer superior glycemic control over SGLT2 inhibitors alone. Future clinical trials should investigate the potential of repurposing CETP inhibitors for metabolic disease treatment, providing an oral therapeutic option that could benefit high-risk patients before they require injectable therapies like insulin or glucagon-like peptide-1 (GLP-1) receptor agonists.
Therapeutic implications for sphingolipid metabolism in metabolic dysfunction-associated steatohepatitis
Authors: Ramos-Molina Bruno , Rossell Joana , Pérez-Montes de Oca Alejandra , Pardina Eva , Genua Idoia , Rojo-López Marina I. , Julián María Teresa , Alonso Núria , Julve Josep , Mauricio Didac
Published: June 2024

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), a leading cause of chronic liver disease, has increased worldwide along with the epidemics of obesity and related dysmetabolic conditions characterized by impaired glucose metabolism and insulin signaling, such as type 2 diabetes mellitus (T2D). MASLD can be defined as an excessive accumulation of lipid droplets in hepatocytes that occurs when the hepatic lipid metabolism is totally surpassed. This metabolic lipid inflexibility constitutes a central node in the pathogenesis of MASLD and is frequently linked to the overproduction of lipotoxic species, increased cellular stress, and mitochondrial dysfunction. A compelling body of evidence suggests that the accumulation of lipid species derived from sphingolipid metabolism, such as ceramides, contributes significantly to the structural and functional tissue damage observed in more severe grades of MASLD by triggering inflammatory and fibrogenic mechanisms. In this context, MASLD can further progress to metabolic dysfunction-associated steatohepatitis (MASH), which represents the advanced form of MASLD, and hepatic fibrosis. In this review, we discuss the role of sphingolipid species as drivers of MASH and the mechanisms involved in the disease. In addition, given the absence of approved therapies and the limited options for treating MASH, we discuss the feasibility of therapeutic strategies to protect against MASH and other severe manifestations by modulating sphingolipid metabolism.
Oil and gas development exposure and atrial fibrillation exacerbation: a retrospective study of atrial fibrillation exacerbation using Colorado's all payer claims dataset
Authors: McKenzie Lisa M. , Allshouse William B. , Abrahams Barbara , Tompkins Christine
Published: June 2024

Introduction

Emerging risk factors for atrial fibrillation (AF) incidence and episodes (exacerbation), the most common and clinically significant cardiac arrhythmia, include air and noise pollution, both of which are emitted during oil and natural gas (O&G) well site development.

Methods

We evaluated AF exacerbation risk and proximity to O&G well site development by employing a novel data source and interrupted time-series design. We retrospectively followed 1,197 AF patients living within 1-mile of an O&G well site (at-risk of exposure) and 9,764 patients living >2 miles from any O&G well site (unexposed) for AF claims in Colorado's All Payer Claims Dataset before, during, and after O&G well site development. We calculated AF exacerbation risk with multi-failure survival analysis.

Results

The analysis of the total study population does not provide strong evidence of an association between AF exacerbation and proximity to O&G wells sites during (HR = 1.07, 95% CI: 0.94, 1.22) or after (HR = 1.01, 95% CI: 0.88, 1.16) development. However, AF exacerbation risk differed by patient age and sex. In patients >80 years living within 0.39 miles (2,059 feet) of O&G well site development, AF exacerbation risk increased by 83% (HR = 1.83, 95% CI: 1.25, 2.66) and emergency room visits for an AF event doubled (HR = 2.55, 95% CI: 1.50, 4.36) during development, with risk increasing with proximity. In female patients living within 0.39 miles of O&G well site development, AF exacerbation risk increased by 56% percent (95% CI: 1.13, 2.15) during development. AF exacerbation risk did not persist past the well development period. We did not observe increased AF exacerbation risk in younger or male patients.

Discussion

The prospect that proximity to O&G well site development, a significant noise and air pollution source, may increase AF exacerbation risk in older and female AF patients requires attention. These findings support appropriate patient education to help mitigate risk and development of mitigation strategies and regulations to protect the health of populations in O&G development regions.
Husband's intention to support during pregnancy for the use of maternity waiting home in Jimma Zone, Southwest, Ethiopia: a community-based cross-sectional study
Authors: Aman Mamusha , Bekele Adisu , Abamecha Fira , Lemu Yohannes Kebede , Gizaw Abraham Tamirat
Published: June 2024

Background

Husbands are the primary decision-makers about the place of childbirth. Lack of husbands' support for maternal health care is associated with low maternal waiting home utilization and less is known about the husbands' intention to support their wife's use of maternal waiting homes (MWHs) and underlying beliefs in Ethiopia. This community-based cross-sectional survey aimed to study husbands' intention to support during pregnancy through the use of maternity waiting homes in Jimma Zone, Southwest Ethiopia.

Method

A cross-sectional study was conducted among 396 randomly selected husbands whose wives were pregnant. Interviewer-administered, a structured questionnaire developed based on the Theory of Planned Behavior (TPB) was used to collect the data. Multivariable logistic regression analyses were used to examine the association between behavioral intention and constructs of the theory of planned behavior.

Results

Of the 396 husbands who took part in the study, 42.7% intend to support their partner's use of a maternity waiting home. Intention to support a wife to use a maternity waiting home was associated with subjective norm [AOR = 1.303, 95% CI (1.054, 1.611)] and perceived behavioral control [AOR = 1.446, 95% CI (1.234, 1.695)]. Among the control beliefs, “having childcare”; “having a person who stays with a wife at a maternity waiting home”; and “availability of quality service provided to a wife in the maternity waiting home” significantly separated intenders and non-intenders.

Conclusion

The findings suggest that husbands who perceived more social pressure and felt in control of barriers were more likely to intend to support their partner in using a maternity waiting home. Intervention should focus on underlying normative and control beliefs to improve the husband's intention.
An emerging maestro of immune regulation: how DOT1L orchestrates the harmonies of the immune system
Authors: Kealy Liam , Runting Jessica , Thiele Daniel , Scheer Sebastian
Published: June 2024

The immune system comprises a complex yet tightly regulated network of cells and molecules that play a critical role in protecting the body from infection and disease. The activity and development of each immune cell is regulated in a myriad of ways including through the cytokine milieu, the availability of key receptors, via tailored intracellular signalling cascades, dedicated transcription factors and even by directly modulating gene accessibility and expression; the latter is more commonly known as epigenetic regulation. In recent years, epigenetic regulators have begun to emerge as key players involved in modulating the immune system. Among these, the lysine methyltransferase DOT1L has gained significant attention for its involvement in orchestrating immune cell formation and function. In this review we provide an overview of the role of DOT1L across the immune system and the implications of this role on health and disease. We begin by elucidating the general mechanisms of DOT1L-mediated histone methylation and its impact on gene expression within immune cells. Subsequently, we provide a detailed and comprehensive overview of recent studies that identify DOT1L as a crucial regulator of immune cell development, differentiation, and activation. Next, we discuss the potential mechanisms of DOT1L-mediated regulation of immune cell function and shed light on how DOT1L might be contributing to immune cell homeostasis and dysfunction. We then provide food for thought by highlighting some of the current obstacles and technical limitations precluding a more in-depth elucidation of DOT1L’s role. Finally, we explore the potential therapeutic implications of targeting DOT1L in the context of immune-related diseases and discuss ongoing research efforts to this end. Overall, this review consolidates the current paradigm regarding DOT1L’s role across the immune network and emphasises its critical role in governing the healthy immune system and its potential as a novel therapeutic target for immune-related diseases. A deeper understanding of DOT1L’s immunomodulatory functions could pave the way for innovative therapeutic approaches which fine-tune the immune response to enhance or restore human health.
Spatiotemporal variation in size and abundance of juvenile Chinese mitten crab (Eriocheir sinensis) in Yangtze Estuary
Authors: Wu Yeling , Wang Sikai , Qin Ze , Geng Zhi , Zhao Feng
Published: June 2024

Introduction

Intertidal habitat preferences and spatiotemporal variation in the abundance of juvenile Chinese mitten crab Eriocheir sinensis in Yangtze Estuary are reported.

Methods

The size and abundance of this crab are reported for mud flat, gravel, root belt, and marsh habitats in this estuary’s lower, middle, and upper reaches from June 2021 (spring) to February 2022 (winter) using quadrat method.

Results

Juvenile E. sinensis of carapace length (CL) 5.5 ± 2.1 mm (mean ± standard deviation) were collected; no juveniles were found in February 2022. Crab abundance in root belt and gravel habitats usually exceeded that of marsh habitat; no juveniles were found in mud flat habitat. The greatest abundances and smallest individuals were found when megalopa recruited in early spring (June); juvenile abundance decreased sharply afterwards, and crabs were absent from the intertidal during winter. Size and relative growth rate of juvenile crabs were greater in root belt and gravel habitat than in marsh habitat from June to August. Recruitment primarily drove changes in crab abundance and size during June and July, and temperature best correlated with changes in the winter. Many stage I juveniles (CL < 3.1 mm) occurred in the lower estuarine reaches, while stage III and IV juveniles (CL 3.9–6.5 mm) primarily occurred in the middle and upper estuarine reaches.

Discussion

Although intertidal wetland habitat in Yangtze Estuary is severely degraded and reduced in area, it remains important for recruitment and maintenance of mitten crab populations. An understanding of the habitat requirements of this species will benefit management of this crab resource and the prioritized restoration of intertidal habitat.
Genetic knowledge and attitudes towards genetic testing among final-year medical students at a public university in Ecuador
Authors: Jaramillo-Aguilar Damary S. , Simbaña-Rivera Katherine
Published: June 2024

Background

Genetics plays a crucial role in the field of medicine, offering numerous applications. However, health professionals often have insufficient knowledge in this area. Therefore, it is essential to provide appropriate genetics education during university studies.

Aim

This study aimed to assess the knowledge and attitudes towards genetic testing among final-year medical students at a public university in Ecuador.

Methods

A cross-sectional study was conducted involving final-year medical students from a public university in Ecuador. The third version of the Genetic Literacy and Attitudes Survey was administered between April and May 2022. The study examined sociodemographic characteristics, genetic knowledge, and attitudes towards genetic testing.

Results

The study included 153 medical students, of which 58.2% identified as female. Most participants fell within the age range of 22 to 25 years old (85.0%). Regarding genetic knowledge, three-quarters of the participants (75.2%) demonstrated intermediate proficiency, while only 9.80% possessed a high level of knowledge. Attitudes towards the clinical and therapeutic applications of genetics, scientific advancements, access to conventional medicine, and other related topics were found to be appropriate.

Conclusion

The findings suggest that most final-year medical students at a public university in Ecuador have intermediate genetic knowledge and hold appropriate attitudes towards genetic testing. However, higher education institutions should conduct a comprehensive analysis and restructure their curricula to better prepare students for the medical and technological challenges of the 21st century.
Disease burden, clinical management and unmet treatment need of patients with moderate to severe atopic dermatitis; consensus statements, insights and practices from CERTADE (Central/Eastern EU, Russia, Turkiye AD Experts) Delphi panel
Authors: Trzeciak Magdalena , Rudnicka Lidia , Arenberger Petr , Engin Burhan , L'vov Andrey , Alper Sibel , Alpsoy Erkan , Benáková Nina , Bobko Svetlana , Borlu Murat , Czarnecka-Operacz Magdalena , Elisyutina Olga , Ergun Tulin , Ertam Ilgen , Fedenko Elena , Filipovská Olga , Fomina Daria , Gadzhigoroeva Aida , Kojanová Martina , Lesiak Aleksandra , Michenko Anna , Murashkin Nikolay , Owczarek Witold , Özkaya Esen , Plzáková Zuzana , Reich Adam , Selerova Marie , Gurbuz Burcu A.
Published: June 2024

Background

There is limited insight into the current disease burden and everyday clinical management of moderate-to- severe AD in Poland, Czechia, Russia, and Turkiye. Therefore, this study aimed to get information-driven insights regarding the current disease burden and clinical management of patients with moderate-to-severe AD with common and differentiating aspects of the patient journey and establish a consensus.

Methods

In this modified 2-round Delphi panel, 133 questions were asked in total to 27 dermatologists. A consensus was achieved when 70% of the panel members strongly agreed or agreed (or strongly disagreed or disagreed) with an item. Statements with <40% agreement dropped from the Delphi rounds and were not repeated.

Results

The results state that AD has a significant impact on the quality of life for both patients and their families with social and economic consequences in these countries. While there were significant dissimilarities regarding the current treatment approach by preference order and treatment duration among participants, there was also a high percentage of consensus on literature and guideline-based statements. Current topical therapies and the immune response modifiers were not found to be sufficient by panelists to cover the therapeutic needs of patients with moderate-to-severe AD. Moreover, panelists highlighted the significant burden of adverse events with the off-label use of currently available immunosuppressants.

Conclusions

These results underlined that there is a significant disease burden with an unmet treatment need for patients with moderate-to-severe AD in Poland, Czechia, Russia, and Turkiye.
Combined transcriptomic and metabolomic analysis revealed that pH changes affected the expression of carbohydrate and ribosome biogenesis-related genes in Aspergillus niger SICU-33
Authors: Zhang Runji , Chen Yulan , Wang Wenxian , Chen Juan , Liu Dongyang , Zhang Lingzi , Xiang Quanju , Zhao Ke , Ma Menggen , Yu Xiumei , Chen Qiang , Penttinen Petri , Gu Yunfu
Published: June 2024

The process of carbohydrate metabolism and genetic information transfer is an important part of the study on the effects of the external environment on microbial growth and development. As one of the most significant environmental parameters, pH has an important effect on mycelial growth. In this study, the effects of environmental pH on the growth and nutrient composition of Aspergillus niger (A. niger) filaments were determined. The pH values of the medium were 5, 7, and 9, respectively, and the molecular mechanism was further investigated by transcriptomics and metabolomics methods. The results showed that pH 5 and 9 significantly inhibited filament growth and polysaccharide accumulation of A. niger. Further, the mycelium biomass of A. niger and the crude polysaccharide content was higher when the medium's pH was 7. The DEGs related to ribosome biogenesis were the most abundant, and the downregulated expression of genes encoding XRN1, RRM, and RIO1 affected protein translation, modification, and carbohydrate metabolism in fungi. The dynamic changes of pargyline and choline were in response to the oxidative metabolism of A. niger SICU-33. The ribophorin_I enzymes and DL-lactate may be important substances related to pH changes during carbohydrate metabolism of A.niger SICU-33. The results of this study provide useful transcriptomic and metabolomic information for further analyzing the bioinformatic characteristics of A. niger and improving the application in ecological agricultural fermentation.
Advances in the immunoescape mechanisms exploited by alphaherpesviruses
Authors: Wang Yimin , Ma Caoyuan , Wang Shan , Wu Hongxia , Chen Xuanqi , Ma Jinyou , Wang Lei , Qiu Hua-Ji , Sun Yuan
Published: June 2024

Alphaherpesviruses, categorized as viruses with linear DNA composed of two complementary strands, can potentially to induce diseases in both humans and animals as pathogens. Mature viral particles comprise of a core, capsid, tegument, and envelope. While herpesvirus infection can elicit robust immune and inflammatory reactions in the host, its persistence stems from its prolonged interaction with the host, fostering a diverse array of immunoescape mechanisms. In recent years, significant advancements have been achieved in comprehending the immunoescape tactics employed by alphaherpesviruses, including pseudorabies virus (PRV), herpes simplex virus (HSV), varicella-zoster virus (VZV), feline herpesvirus (FeHV), equine herpesvirus (EHV), and caprine herpesvirus type I (CpHV-1). Researchers have unveiled the intricate adaptive mechanisms existing between viruses and their natural hosts. This review endeavors to illuminate the research advancements concerning the immunoescape mechanisms of alphaherpesviruses by delineating the pertinent proteins and genes involved in virus immunity. It aims to furnish valuable insights for further research on related mechanisms and vaccine development, ultimately contributing to virus control and containment efforts.
Gut microbiota characteristics of colorectal cancer patients in Hubei, China, and differences with cohorts from other Chinese regions
Authors: Shi Jianguo , Shen Hexiao , Huang Hui , Zhan Lifang , Chen Wei , Zhou Zhuohui , Lv Yongling , Xiong Kai , Jiang Zhiwei , Chen Qiyi , Liu Lei
Published: June 2024

The research on the correlation or causality between gut microbiota and the occurrence, development, and treatment of colorectal cancer (CRC) is receiving increasing emphasis. At the same time, the incidence and mortality of colorectal cancer vary among individuals and regions, as does the gut microbiota. In order to gain a better understanding of the characteristics of the gut microbiota in CRC patients and the differences between different regions, we initially compared the gut microbiota of 25 CRC patients and 26 healthy controls in the central region of China (Hubei Province) using 16S rRNA high-throughput sequencing technology. The results showed that Corynebacterium, Enterococcus, Lactobacillus, and Escherichia-Shigella were significantly enriched in CRC patients. In addition, we also compared the potential differences in functional pathways between the CRC group and the healthy control group using PICRUSt’s functional prediction analysis. We then analyzed and compared it with five cohort studies from various regions of China, including Central, East, and Northeast China. We found that geographical factors may affect the composition of intestinal microbiota in CRC patients. The composition of intestinal microbiota is crucial information that influences colorectal cancer screening, early detection, and the prediction of CRC treatment outcomes. This emphasizes the importance of conducting research on CRC-related gut microbiota in various regions of China.
Targeted drug release from stable and safe ultrasound-sensitive nanocarriers
Authors: Wilson Matthew G. , Parikh Aarav , Dara Audri , Beaver Alexander S. , Kubanek Jan
Published: June 2024

Targeted delivery of medication has the promise of increasing the effectiveness and safety of current systemic drug treatments. Focused ultrasound is emerging as noninvasive and practical energy for targeted drug release. However, it has yet to be determined which nanocarriers and ultrasound parameters can provide both effective and safe release. Perfluorocarbon nanodroplets have the potential to achieve these goals, but current approaches have either been effective or safe, but not both. We found that nanocarriers with highly stable perfluorocarbon cores mediate effective drug release so long as they are activated by ultrasound of sufficiently low frequency. We demonstrate a favorable safety profile of this formulation in a non-human primate. To facilitate translation of this approach into humans, we provide an optimized method for manufacturing the nanocarriers. This study provides a recipe and release parameters for effective and safe drug release from nanoparticle carriers in the body part specified by focused ultrasonic waves.
A dysphagia model with denervation of the pharyngeal constrictor muscles in guinea pigs: functional evaluation of swallowing
Authors: Hashimoto Keiko , Sugiyama Yoichiro , Kaneko Mami , Kinoshita Shota , Yamamoto Ryota , Ishida Tomoya , Umezaki Toshiro , Hirano Shigeru
Published: June 2024

Introduction

Swallowing impairment is a crucial issue that can lead to aspiration, pneumonia, and malnutrition. Animal models are useful to reveal pathophysiology and to facilitate development of new treatments for dysphagia caused by many diseases. The present study aimed to develop a new dysphagia model with reduced pharyngeal constriction during pharyngeal swallowing.

Methods

We analyzed the dynamics of pharyngeal swallowing over time with the pharyngeal branches of the vagus nerve (Ph-X) bilaterally or unilaterally transected, using videofluoroscopic assessment of swallowing in guinea pigs. We also evaluated the detailed anatomy of the pharyngeal constrictor muscles after the denervation.

Results

Videofluoroscopic examination of swallowing showed a significant increase in the pharyngeal area during swallowing after bilateral and unilateral sectioning of the Ph-X. The videofluoroscopy also showed significantly higher pharyngeal transit duration for bilateral and unilateral section groups. The thyropharyngeal muscle on the sectioned side was significantly thinner than that on the intact side. In contrast, the thickness of the cricopharyngeal muscles on the sectioned and intact sides were not significantly different. The mean thickness of the bilateral thyropharyngeal muscles showed a linear correlation to the pharyngeal area and pharyngeal transit duration.

Discussion

Data obtained in this study suggest that denervation of the Ph-X could influence the strength of pharyngeal contraction during pharyngeal swallowing in relation to thickness of the pharyngeal constrictor muscles, resulting in a decrease in bolus speed. This experimental model may provide essential information (1) for the development of treatments for pharyngeal dysphagia and (2) on the mechanisms related to the recovery process, reinnervation, and nerve regeneration following injury and swallowing impairment possibly caused by medullary stroke, neuromuscular disease, or surgical damage from head and neck cancer.
Psychedelics in developmental stuttering to modulate brain functioning: a new therapeutic perspective?
Authors: Pasculli Giuseppe , Busan Pierpaolo , Jackson Eric S. , Alm Per A. , De Gregorio Danilo , Maguire Gerald A. , Goodwin Guy M. , Gobbi Gabriella , Erritzoe David , Carhart-Harris Robin L.
Published: June 2024

Developmental stuttering (DS) is a neurodevelopmental speech-motor disorder characterized by symptoms such as blocks, repetitions, and prolongations. Persistent DS often has a significant negative impact on quality of life, and interventions for it have limited efficacy. Herein, we briefly review existing research on the neurophysiological underpinnings of DS -specifically, brain metabolic and default mode/social-cognitive networks (DMN/SCN) anomalies- arguing that psychedelic compounds might be considered and investigated (e.g., in randomized clinical trials) for treatment of DS. The neural background of DS is likely to be heterogeneous, and some contribution from genetically determinants of metabolic deficiencies in the basal ganglia and speech-motor cortical regions are thought to play a role in appearance of DS symptoms, which possibly results in a cascade of events contributing to impairments in speech-motor execution. In persistent DS, the difficulties of speech are often linked to a series of associated aspects such as social anxiety and social avoidance. In this context, the SCN and DMN (also influencing a series of fronto-parietal, somato-motor, and attentional networks) may have a role in worsening dysfluencies. Interestingly, brain metabolism and SCN/DMN connectivity can be modified by psychedelics, which have been shown to improve clinical evidence of some psychiatric conditions (e.g., depression, post-traumatic stress disorder, etc.) associated with psychological constructs such as rumination and social anxiety, which also tend to be present in persistent DS. To date, while there have been no controlled trials on the effects of psychedelics in DS, anecdotal evidence suggests that these agents may have beneficial effects on stuttering and its associated characteristics. We suggest that psychedelics warrant investigation in DS.
The mechanism of human color vision and potential implanted devices for artificial color vision
Authors: Zhang Bingao , Zhang Rong , Zhao Jingjin , Yang Jiarui , Xu Shengyong
Published: June 2024

Vision plays a major role in perceiving external stimuli and information in our daily lives. The neural mechanism of color vision is complicated, involving the co-ordinated functions of a variety of cells, such as retinal cells and lateral geniculate nucleus cells, as well as multiple levels of the visual cortex. In this work, we reviewed the history of experimental and theoretical studies on this issue, from the fundamental functions of the individual cells of the visual system to the coding in the transmission of neural signals and sophisticated brain processes at different levels. We discuss various hypotheses, models, and theories related to the color vision mechanism and present some suggestions for developing novel implanted devices that may help restore color vision in visually impaired people or introduce artificial color vision to those who need it.
The role of Foxo3a in neuron-mediated cognitive impairment
Authors: Liu Qin-Qin , Wu Gui-Hua , Wang Xiao-Chun , Xiong Xiao-Wen , Rui-Wang  , Yao Bao-Le
Published: June 2024

Cognitive impairment (COI) is a prevalent complication across a spectrum of brain disorders, underpinned by intricate mechanisms yet to be fully elucidated. Neurons, the principal cell population of the nervous system, orchestrate cognitive processes and govern cognitive balance. Extensive inquiry has spotlighted the involvement of Foxo3a in COI. The regulatory cascade of Foxo3a transactivation implicates multiple downstream signaling pathways encompassing mitochondrial function, oxidative stress, autophagy, and apoptosis, collectively affecting neuronal activity. Notably, the expression and activity profile of neuronal Foxo3a are subject to modulation via various modalities, including methylation of promoter, phosphorylation and acetylation of protein. Furthermore, upstream pathways such as PI3K/AKT, the SIRT family, and diverse micro-RNAs intricately interface with Foxo3a, engendering alterations in neuronal function. Through several downstream routes, Foxo3a regulates neuronal dynamics, thereby modulating the onset or amelioration of COI in Alzheimer’s disease, stroke, ischemic brain injury, Parkinson’s disease, and traumatic brain injury. Foxo3a is a potential therapeutic cognitive target, and clinical drugs or multiple small molecules have been preliminarily shown to have cognitive-enhancing effects that indirectly affect Foxo3a. Particularly noteworthy are multiple randomized, controlled, placebo clinical trials illustrating the significant cognitive enhancement achievable through autophagy modulation. Here, we discussed the role of Foxo3a in neuron-mediated COI and common cognitively impaired diseases.
Gender differences in the association between dietary protein intake and constipation: findings from NHANES
Authors: Hong Yongping , Shen Hongchen , Chen Xingxing , Li Guofeng
Published: June 2024

Purpose

Dietary factors play a crucial role in the development and management of chronic constipation, yet the relationship between dietary protein intake and constipation remains underexplored. This study aims to investigate the association between dietary protein intake and the prevalence of constipation among American adults, with a focus on potential gender differences, using large-scale national data.

Materials and methods

Data from 14,048 participants aged 20 and above (7,072 men and 6,976 women) from the National Health and Nutrition Examination Survey (NHANES) 2005–2010 were analyzed. The Bristol Stool Form Scale’s types 1 (separate hard lumps, resembling nuts) and 2 (sausage-shaped, but lumpy) were used to define constipation. A 24-h dietary recall technique was used to measure dietary protein intake. After controlling for covariates, the association between protein consumption and constipation risk was examined using multivariable logistic regression, smooth curve fitting, and testing for gender interaction effects. We then further determined the threshold effect between dietary protein intake and constipation risk.

Results

Constipation was present in 7.49% of people overall, with a higher proportion among women (10.19%) than among males (4.82%). In men, higher protein intake was significantly associated with a lower rate of constipation. However, in women, higher protein intake correlated with an increased risk of constipation, and the interaction between gender was significant (P for interaction = 0.0298). These results were corroborated by smooth curve fits, which also demonstrated a dose–response effect. Further threshold effect analysis showed that the turning points of dietary protein intake differed between male and female participants (119.42 gm/day for men; 40.79 gm/day for women).

Conclusion

The association between dietary protein intake and constipation was different in different genders with threshold effect. For men, moderately increasing protein intake could be beneficial, while for women, exceeding a certain level may increase the risk of constipation. These insights are crucial for guiding dietary protein recommendations for different genders and have significant clinical implications.
Effects of maternal advanced lipoxidation end products diet on the glycolipid metabolism and gut microbiota in offspring mice
Authors: Pang Wenwen , Zhang Bowei , Zhang Junshi , Chen Tianyi , Han Qiurong , Yang Zhen
Published: June 2024

Introduction

Dietary advanced lipoxidation end products (ALEs), which are abundant in heat-processed foods, could induce lipid metabolism disorders. However, limited studies have examined the relationship between maternal ALEs diet and offspring health.

Methods

To investigate the transgenerational effects of ALEs, a cross-generation mouse model was developed. The C57BL/6J mice were fed with dietary ALEs during preconception, pregnancy and lactation. Then, the changes of glycolipid metabolism and gut microbiota of the offspring mice were analyzed.

Results

Maternal ALEs diet not only affected the metabolic homeostasis of dams, but also induced hepatic glycolipid accumulation, abnormal liver function, and disturbance of metabolism parameters in offspring. Furthermore, maternal ALEs diet significantly upregulated the expression of TLR4, TRIF and TNF-α proteins through the AMPK/mTOR/PPARα signaling pathway, leading to dysfunctional glycolipid metabolism in offspring. In addition, 16S rRNA analysis showed that maternal ALEs diet was capable of altered microbiota composition of offspring, and increased the Firmicutes/Bacteroidetes ratio.

Discussion

This study has for the first time demonstrated the transgenerational effects of maternal ALEs diet on the glycolipid metabolism and gut microbiota in offspring mice, and may help to better understand the adverse effects of dietary ALEs.
CT, MRI, and PET/CT imaging features of thoracic spine epithelioid hemangioma: a retrospective observational study
Authors: Hu Xianwen , Li Xiaotian , Xiong Zujiang , Li Dandan , Cai Jiong , Wang Pan
Published: June 2024

Introduction

Epithelioid hemangioma (EH) is an intermediate locally aggressive tumor that consists of epithelioid cells and endothelial cell differentiation, which can occur at any age, but is most common between the ages of 30 and 40 years. EH in the thoracic spine is rare, and accurate diagnosis is critical to treatment planning. Our aim was to explore the imaging and clinical data of thoracic spine EH to improve the understanding of this rare disease.

Methods

From January 1, 2018 to June 30, 2023, a database of thoracic spine masses was retrospectively reviewed. Five patients with histologically proven thoracic spine EH and complete imaging available were identified and analyzed. Computed tomography (CT) and magnetic resonance imaging (MRI) findings were evaluated separately by two radiologists with more than 10 years of experience. Positron emission tomography (PET)/CT was conducted by two nuclear medicine diagnostic technologists with at least 5 years of experience.

Results

The patients included three male and two female patients aged 23 to 56 years (mean age was 38.4 ± 14.3 years). All patients underwent CT, MRI, and 18F-FDG PET/CT examination before treatment. Four patients were limited to one vertebral involvement, only one patient had multiple vertebral involvement, and all tumors involved the accessories, including one involving the posterior ribs. The maximum diameter of the tumor ranged from 2.7 to 4.3.

Conclusions

CT, MRI, and 18F-FDG PET/CT findings of thoracic spine EH have certain characteristics, and understanding these imaging findings will help to obtain accurate diagnosis before surgery.
Global burden and trends of leukemia attributable to high body mass index risk in adults over the past 30 years
Authors: Xiao Hang , Hu Xiao , Li Pengfei , Deng Jianchuan
Published: June 2024

Background

High BMI (Body Mass Index) is a significant factor impacting health, with a clear link to an increased risk of leukemia. Research on this topic is limited. Understanding the epidemiological trends of leukemia attributable to high BMI risk is crucial for disease prevention and patient support.

Methods

We obtained the data from the Global Burden of Disease Study, analyzing the ASR (age-standardized rates), including ASDR (age-standardized death rate) and age-standardized disability-adjusted life years (DALYs) rate, and estimated annual percentage change (EAPC) by gender, age, country, and region from 1990 to 2019.

Results

In 2019, deaths and DALYs have significantly increased to 21.73 thousand and 584.09 thousand. The global age-standardized death and DALYs rates have slightly increased over the past 30 years (EAPCs: 0.34 and 0.29). Among four common leukemia subtypes, only CML (Chronic Myeloid Leukemia) exhibited a significant decrease in ASDR and age-standardized DALYs rate, with EAPC of -1.74 and -1.52. AML (Acute Myeloid Leukemia) showed the most pronounced upward trend in ASDR, with an EAPC of 1.34. These trends vary by gender, age, region, and national economic status. Older people have been at a significantly greater risk. Females globally have borne a higher burden. While males have shown an increasing trend. The regions experiencing the greatest growth in ASR were South Asia. The countries with the largest increases were Equatorial Guinea. However, It is worth noting that there may be variations among specific subtypes of leukemia. Regions with high Socio-demographic Index (SDI) have had the highest ASR, while low-middle SDI regions have shown the greatest increase in these rates. All ASRs values have been positively correlated with SDI, but there has been a turning point in medium to high SDI regions.

Conclusions

Leukemia attributable to high BMI risk is gradually becoming a heavier burden globally. Different subtypes of leukemia have distinct temporal and regional patterns. This study’s findings will provide information for analyzing the worldwide disease burden patterns and serve as a basis for disease prevention, developing suitable strategies for the modifiable risk factor.
Effects of different doses of dexmedetomidine combined with sufentanil in intravenous controlled analgesia after Salter osteotomy in children
Authors: He Zhiwei , Ni Huanhuan , Wang Wei
Published: June 2024

Background

This study aimed to investigate the effect of different doses of dexmedetomidine combined with sufentanil on postoperative analgesia in developmental hip dislocation in children after Salter osteotomy.

Methods

The clinical data of 98 children with developmental hip dislocation, who underwent Salter osteotomy in our center between January 2020 and February 2023, were selected. The children were randomly divided into four groups based on the application of patient-controlled intravenous analgesia (sufentanil + granisetron ± dexmedetomidine). All children received 1 µg/kg/day of sufentanil and 3 mg of granisetron. Group A did not receive dexmedetomidine, and Groups B, C, and D received 0.5, 0.75, and 1.0 µg/kg/day of dexmedetomidine, respectively. The pain indicators and immune factor levels of children in each group were compared.

Results

The heart rate (HR) and respiratory rate (RR) 2 h after operation in Groups C and D were significantly lower than those in Groups A and B (P < 0.05). The pain scores decreased over time after treatment in all groups. When compared at the same time point, children in Group D had the lowest pain scores, which were significantly lower than the other three groups (P < 0.05). The total consumption of sufentanil in Groups C and D was significantly lower than that in Group A (P < 0.05). On the first day after surgery, the children in Group D had lower levels of serum adrenocorticotropic hormone, interleukin-6, and corticosterone than those in Group A (P < 0.05).

Conclusion

Administration of 1.0 µg/kg/day of dexmedetomidine combined with sufentanil in intravenous controlled analgesia after Salter osteotomy for developmental hip dislocation in children has a better analgesic effect, less consumption of sufentanil, and low incidence of opioid adverse reactions.
Pediatric dilated cardiomyopathy: a review of current clinical approaches and pathogenesis
Authors: Malinow Ian , Fong Daniel C. , Miyamoto Matthew , Badran Sarah , Hong Charles C.
Published: June 2024

Pediatric dilated cardiomyopathy (DCM) is a rare, yet life-threatening cardiovascular condition characterized by systolic dysfunction with biventricular dilatation and reduced myocardial contractility. Therapeutic options are limited with nearly 40% of children undergoing heart transplant or death within 2 years of diagnosis. Pediatric patients are currently diagnosed based on correlating the clinical picture with echocardiographic findings. Patient age, etiology of disease, and parameters of cardiac function significantly impact prognosis. Treatments for pediatric DCM aim to ameliorate symptoms, reduce progression of disease, and prevent life-threatening arrhythmias. Many therapeutic agents with known efficacy in adults lack the same evidence in children. Unlike adult DCM, the pathogenesis of pediatric DCM is not well understood as approximately two thirds of cases are classified as idiopathic disease. Children experience unique gene expression changes and molecular pathway activation in response to DCM. Studies have pointed to a significant genetic component in pediatric DCM, with variants in genes related to sarcomere and cytoskeleton structure implicated. In this regard, pediatric DCM can be considered pediatric manifestations of inherited cardiomyopathy syndromes. Yet exciting recent studies in infantile DCM suggest that this subset has a distinct etiology involving defective postnatal cardiac maturation, such as the failure of programmed centrosome breakdown in cardiomyocytes. Improved knowledge of pathogenesis is central to developing child-specific treatment approaches. This review aims to discuss the established biological pathogenesis of pediatric DCM, current clinical guidelines, and promising therapeutic avenues, highlighting differences from adult disease. The overarching goal is to unravel the complexities surrounding this condition to facilitate the advancement of novel therapeutic interventions and improve prognosis and overall quality of life for pediatric patients affected by DCM.
Diagnostic accuracy of serum calprotectin measured by CLIA and EIA in juvenile idiopathic arthritis: a proof-of-concept study
Authors: Codes-Méndez Helena , Magallares-López Berta , Park Hye-Sang , Mariscal Anaís , Juárez Cándido , Boronat Susana , Martínez-Martínez Laura , Corominas Hector
Published: June 2024

Objective

C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are used to assess disease activity in juvenile idiopathic arthritis (JIA). However, because these biomarkers do not always differentiate between active and inactive disease, there is a need for alternative markers such as serum calprotectin (sCal). The main aim of this proof-of-concept study was to assess the diagnostic accuracy of sCal in patients with JIA. Secondary aims were to identify the optimal sCal cut-off levels to define active disease and evaluate the association between these biomarkers and disease activity status.

Methods

Serum samples were obtained from 25 pediatric patients with JIA. Serum calprotectin levels were determined by two different assays, the QUANTA FLASH chemiluminescence immunoassay (CLIA) from Inova Diagnostics and the solid-phase enzyme immunoassay (EIA) from Bühlmann Laboratories. Diagnostic accuracy was assessed for sCal CLIA, sCal EIA, CRP, and ESR. The results obtained by the CLIA and EIA methodologies were compared. We also evaluated the association between the individual each biomarkers (sCal CLIA, sCal EIA, CRP, and ESR) and disease activity (according to JADAS-27 criteria and the ACR criteria modified by Anink and colleagues).

Results

For both sCal assays (CLIA and EIA), the optimal cut-off level (ROC analysis) was the same (2.3 µg/ml). Serum calprotectin levels measured by CLIA and EIA were strongly correlated with each other (Kendall's tau-b, 0.71; p < 0.001). Compared to ESR and CRP, sCal CLIA and EIA were both more accurate (i.e., greater sensitivity) in identifying patients with active disease. By contrast, ESR and CRP were more effective in identifying patients in remission (i.e., better specificity).

Conclusion

This proof-of-concept study shows that determination of serum calprotectin levels with CLIA or EIA can accurately identify the presence of active disease in patients with JIA.
An updated review of the pharmacological effects and potential mechanisms of hederagenin and its derivatives
Authors: Zhang Huize , Li Yong , Liu Yi
Published: June 2024

Hederagenin (HG) is a natural pentacyclic triterpenoid that can be isolated from various medicinal herbs. By modifying the structure of HG, multiple derivatives with superior biological activities and safety profiles have been designed and synthesized. Accumulating evidence has demonstrated that HG and its derivatives display multiple pharmacological activities against cancers, inflammatory diseases, infectious diseases, metabolic diseases, fibrotic diseases, cerebrovascular and neurodegenerative diseases, and depression. Previous studies have confirmed that HG and its derivatives combat cancer by exerting cytotoxicity, inhibiting proliferation, inducing apoptosis, modulating autophagy, and reversing chemotherapy resistance in cancer cells, and the action targets involved mainly include STAT3, Aurora B, KIF7, PI3K/AKT, NF-κB, Nrf2/ARE, Drp1, and P-gp. In addition, HG and its derivatives antagonize inflammation through inhibiting the production and release of pro-inflammatory cytokines and inflammatory mediators by regulating inflammation-related pathways and targets, such as NF-κB, MAPK, JAK2/STAT3, Keap1-Nrf2/HO-1, and LncRNA A33/Axin2/β-catenin. Moreover, anti-pathogen, anti-metabolic disorder, anti-fibrosis, neuroprotection, and anti-depression mechanisms of HG and its derivatives have been partially elucidated. The diverse pharmacological properties of HG and its derivatives hold significant implications for future research and development of new drugs derived from HG, which can lead to improved effectiveness and safety profiles.