bluuebunny/crossref_metadata_2025 huggingface dataset:
Normal cardiac dimensions by magnetic resonance imaging and topographic anatomy of the adult arabian one-humped camel (Camelus dromedarius)
Authors: Aref Mohamed , El-Zahar Heba , Mandour Ahmed S. , Abd-Elhafeez Hanan H. , Khormi Mohsen. A , AbdRabou Mervat A. , Abdelbaset-Ismail Ahmed
Published: June 2024

Background

Dromedaries’ normal heart architecture and size have not been adequately examined utilizing magnetic resonance imaging (MRI) and topographic anatomy.

Result

we aimed to investigate the regular appearance of the heart and its dimensions, using MRI and cross-sectional anatomy, in mature Arabian one-humped camels (Camelus dromedarius). We also analyzed hematological and cardiac biochemical markers. MRI scans were conducted on twelve camel heart cadavers using a closed 1.5-Tesla magnet with fast spin echo (FSE) weighted sequences. Subsequently, the hearts were cross-sectionally sliced. Additionally, hematobiochemical studies were conducted on ten mature live camels. The study analyzed standard cardiac dimensions including HL, BW, RA, LA, RV, LV, IVS, LAD, RAD, RVD, AoD, TCVD, and MVD. The results showed a strong positive correlation between the cardiac dimensions obtained from both gross analysis and MR images, with no significant difference between them. On both gross and MRI images, the usual structures of the heart were identified and labeled. Along with the cardiac markers (creatine kinase and troponin), the average hematological values and standard biochemical parameters were also described.

Conclusion

According to what we know, this investigation demonstrates, for the first time the typical heart structures and dimensions of the heart in dromedaries, and it could serve as a basis for diagnosing cardiac disorders in these animals.
Immunoglobulin and T cell receptor repertoire changes induced by a prototype vaccine against Chagas disease in naïve rhesus macaques
Authors: Dumonteil Eric , Tu Weihong , Desale Hans , Goff Kelly , Marx Preston , Ortega-Lopez Jaime , Herrera Claudia
Published: June 2024

Background

A vaccine against Trypanosoma cruzi, the agent of Chagas disease, would be an excellent additional tool for disease control. A recombinant vaccine based on Tc24 and TSA1 parasite antigens was found to be safe and immunogenic in naïve macaques.

Methods

We used RNA-sequencing and performed a transcriptomic analysis of PBMC responses to vaccination of naïve macaques after each vaccine dose, to shed light on the immunogenicity of this vaccine and guide the optimization of doses and formulation. We identified differentially expressed genes and pathways and characterized immunoglobulin and T cell receptor repertoires.

Results

RNA-sequencing analysis indicated a clear transcriptomic response of PBMCs after three vaccine doses, with the up-regulation of several immune cell activation pathways and a broad non-polarized immune profile. Analysis of the IgG repertoire showed that it had a rapid turnover with novel IgGs produced following each vaccine dose, while the TCR repertoire presented several persisting clones that were expanded after each vaccine dose.

Conclusions

These data suggest that three vaccine doses may be needed for optimum immunogenicity and support the further evaluation of the protective efficacy of this vaccine.
High stress hyperglycemia ratio predicts adverse clinical outcome in patients with coronary three-vessel disease: a large-scale cohort study
Authors: Qiao Zheng , Bian Xiaohui , Song Chenxi , Zhang Rui , Yuan Sheng , Lin Zhangyu , Zhu Chenggang , Liu Qianqian , Ma Wenjun , Dou Kefei
Published: June 2024

Background

Coronary three-vessel disease (CTVD) accounts for one-third of the overall incidence of coronary artery disease, with heightened mortality rates compared to single-vessel lesions, including common trunk lesions. Dysregulated glucose metabolism exacerbates atherosclerosis and increases cardiovascular risk. The stress hyperglycemia ratio (SHR) is proposed as an indicator of glucose metabolism status but its association with cardiovascular outcomes in CTVD patients undergoing percutaneous coronary intervention (PCI) remains unclear.

Methods

10,532 CTVD patients undergoing PCI were consecutively enrolled. SHR was calculated using the formula: admission blood glucose (mmol/L)/[1.59×HbA1c (%)–2.59]. Patients were divided into two groups (SHR Low and SHR High) according to the optimal cutoff value of SHR. Multivariable Cox regression models were used to assess the relationship between SHR and long-term prognosis. The primary endpoint was cardiovascular (CV) events, composing of cardiac death and non-fatal myocardial infarction (MI).

Results

During the median follow-up time of 3 years, a total of 279 cases (2.6%) of CV events were recorded. Multivariable Cox analyses showed that high SHR was associated with a significantly higher risk of CV events [Hazard Ratio (HR) 1.99, 95% Confidence interval (CI) 1.58–2.52, P < 0.001). This association remained consistent in patients with (HR 1.50, 95% CI 1.08–2.10, P = 0.016) and without diabetes (HR 1.97, 95% CI 1.42–2.72, P < 0.001). Additionally, adding SHR to the base model of traditional risk factors led to a significant improvement in the C-index, net reclassification and integrated discrimination.

Conclusions

SHR was a significant predictor for adverse CV outcomes in CTVD patients with or without diabetes, which suggested that it could aid in the risk stratification in this particular population regardless of glucose metabolism status.
cFLIP in the molecular regulation of astroglia-driven neuroinflammation in experimental glaucoma
Authors: Yang Xiangjun , Zeng Qun , İnam Maide Gözde , İnam Onur , Lin Chyuan-Sheng , Tezel Gülgün
Published: June 2024

Background

Recent experimental studies of neuroinflammation in glaucoma pointed to cFLIP as a molecular switch for cell fate decisions, mainly regulating cell type-specific caspase-8 functions in cell death and inflammation. This study aimed to determine the importance of cFLIP for regulating astroglia-driven neuroinflammation in experimental glaucoma by analyzing the outcomes of astroglia-targeted transgenic deletion of cFLIP or cFLIPL.

Methods

Glaucoma was modeled by anterior chamber microbead injections to induce ocular hypertension in mouse lines with or without conditional deletion of cFLIP or cFLIPL in astroglia. Morphological analysis of astroglia responses assessed quantitative parameters in retinal whole mounts immunolabeled for GFAP and inflammatory molecules or assayed for TUNEL. The molecular analysis included 36-plexed immunoassays of the retina and optic nerve cytokines and chemokines, NanoString-based profiling of inflammation-related gene expression, and Western blot analysis of selected proteins in freshly isolated samples of astroglia.

Results

Immunoassays and immunolabeling of retina and optic nerve tissues presented reduced production of various proinflammatory cytokines, including TNFα, in GFAP/cFLIP and GFAP/cFLIPL relative to controls at 12 weeks of ocular hypertension with no detectable alteration in TUNEL. Besides presenting a similar trend of the proinflammatory versus anti-inflammatory molecules displayed by immunoassays, NanoString-based molecular profiling detected downregulated NF-κB/RelA and upregulated RelB expression of astroglia in ocular hypertensive samples of GFAP/cFLIP compared to ocular hypertensive controls. Analysis of protein expression also revealed decreased phospho-RelA and increased phospho-RelB in parallel with an increase in caspase-8 cleavage products.

Conclusions

A prominent response limiting neuroinflammation in ocular hypertensive eyes with cFLIP-deletion in astroglia values the role of cFLIP in the molecular regulation of glia-driven neuroinflammation during glaucomatous neurodegeneration. The molecular responses accompanying the lessening of neurodegenerative inflammation also seem to maintain astroglia survival despite increased caspase-8 cleavage with cFLIP deletion. A transcriptional autoregulatory response, dampening RelA but boosting RelB for selective expression of NF-κB target genes, might reinforce cell survival in cFLIP-deleted astroglia.
Motivations for using misoprostol for abortion outside the formal healthcare system in Colombia: a qualitative study of women seeking postabortion care in Bogotá and the Coffee Axis
Authors: Ortiz Juliette , Blades Nakeisha , Prada Elena
Published: June 2024

Background

In 2006, a Constitutional Court ruling partially decriminalized abortion in Colombia, allowing the procedure in cases of rape, risk to the health or life of the woman, and fetal malformations incompatible with life. Despite this less prohibitive law, some women and pregnant people preferred self-managing their abortions outside the formal healthcare system, often without accurate information. In 2018, we undertook a study to understand what motivated women to self-manage using medications that they acquired informally. Colombia has since adopted a progressive law in 2022, permitting abortion on request through the 24th week of pregnancy. However, the implementation of this law is still underway. Examining the reasons why women chose to informally self-manage an abortion after 2006 may not only highlight how barriers to legal services persisted at that time, but also could inform strategies to increase knowledge of the current abortion law and improve access to services going forward.

Methods

In-depth interviews were conducted in 2018 with 47 women aged 18 and older who used misoprostol obtained outside of health facilities to induce an abortion, and who were receiving postabortion care in two private clinics. Interviews explored what women knew about the 2006 abortion law which was then in effect, and the reasons why they preferred informal channels for abortion care over formal healthcare services.

Results

Women’s motivations to use misoprostol obtained outside the formal healthcare system were influenced by lack of trust in the healthcare system along with incomplete and inaccurate knowledge of the abortion law. Conversely, women considered misoprostol obtained outside the healthcare system to be effective, affordable, and easier to access.

Conclusions

Obtaining misoprostol outside the formal healthcare system offered a more accessible and appealing prospect for some women given fears of legal repercussion and stigma toward abortion. Though this preference will likely continue despite the more liberal abortion law, strategies should be implemented to broaden knowledge of the recent change in law and to combat misinformation and stigma. This would support knowledge of and access to legal abortion for those who wish to avail themselves of these services.
Ac2-26 reduced the liver injury after cardiopulmonary bypass in rats via AKT1/GSK3β/eNOS pathway
Authors: Xing Xi-chun , Liu Zi-ying , Yang Qing , Jia Bao-wei , Qiu Lin , Zhang Lu-lu , Gao Wei
Published: June 2024

Objective

About 10% of patients after cardiopulmonary bypass (CPB) would undergo acute liver injury, which aggravated the mortality of patients. Ac2-26 has been demonstrated to ameliorate organic injury by inhibiting inflammation. The present study aims to evaluate the effect and mechanism of Ac2-26 on acute liver injury after CPB.

Methods

A total of 32 SD rats were randomized into sham, CPB, Ac, and Ac/AKT1 groups. The rats only received anesthesia, and rats in other groups received CPB. The rats in Ac/AKT1 were pre-injected with the shRNA to interfere with the expression of AKT1. The rats in CPB were injected with saline, and rats in Ac and Ac/AKT1 groups were injected with Ac2-26. After 12 h of CPB, all the rats were sacrificed and the peripheral blood and liver samples were collected to analyze. The inflammatory factors in serum and liver were detected. The liver function was tested, and the pathological injury of liver tissue was evaluated.

Results

Compared with the sham group, the inflammatory factors, liver function, and pathological injury were worsened after CPB. Compared with the CPB group, the Ac2-26 significantly decreased the pro-inflammatory factors and increased the anti-inflammatory factor, improved liver function, and ameliorated the pathological injury. All the therapeutic effects of Ac2-26 were notably attenuated by the shRNA of AKT1. The Ac2-26 increased the GSK3β and eNOS, and this promotion was inhibited by the shRNA.

Conclusion

The Ac2-26 significantly treated the liver injury, inhibited inflammation, and improved liver function. The effect of Ac2-26 on liver injury induced by CPB was partly associated with the promotion of AKT1/GSK3β/eNOS.
Greenhouse gas fluxes of different land uses in mangrove ecosystem of East Kalimantan, Indonesia
Authors: Arifanti Virni Budi , Candra Randi Ade , Putra Chandra Agung Septiadi , Asyhari Adibtya , Gangga Adi , Ritonga Rasis Putra , Ilman Muhammad , Anggoro Aji W. , Novita Nisa
Published: June 2024

Background

Mangrove ecosystems exhibit significant carbon storage and sequestration. Its capacity to store and sequester significant amounts of carbon makes this ecosystem very important for climate change mitigation. Indonesia, owing to the largest mangrove cover in the world, has approximately 3.14 PgC stored in the mangroves, or about 33% of all carbon stored in coastal ecosystems globally. Unfortunately, our comprehensive understanding of carbon flux is hampered by the incomplete repertoire of field measurement data, especially from mangrove ecosystem-rich regions such as Indonesia and Asia Pacific. This study fills the gap in greenhouse gases (GHGs) flux studies in mangrove ecosystems in Indonesia by quantifying the soil CO2 and CH4 fluxes for different land use types in mangrove ecosystems, i.e., secondary mangrove (SM), restored mangrove (RM), pond embankment (PE) and active aquaculture pond (AP). Environmental parameters such as soil pore salinity, soil pore water pH, soil temperature, air temperature, air humidity and rainfall are also measured.

Results

GHG fluxes characteristics varied between land use types and ecological conditions. Secondary mangrove and exposed pond embankment are potential GHG flux sources (68.9 ± 7.0 and 58.5 ± 6.2 MgCO2e ha− 1 yr− 1, respectively). Aquaculture pond exhibits the lowest GHG fluxes among other land use types due to constant inundation that serve as a barrier for the release of GHG fluxes to the atmosphere. We found weak relationships between soil CO2 and CH4 fluxes and environmental parameters.

Conclusions

The data and information on GHG fluxes from different land use types in the mangrove ecosystem will be of importance to accurately assess the potential of the mangrove ecosystem to sequester and emit GHGs. This will support the GHG emission reduction target and strategy that had been set up by the Indonesian Government in its Nationally Determined Contributions (NDC) and Indonesia’s 2030 Forest and Other Land Use (FOLU) Net Sink.
What aspects of the pandemic had the greatest impact on adolescent mental health: duration of lockdown or subjective experience?
Authors: Fujimoto Hiroko , Heywood Anita , Maston Kate , Brown Lyndsay , Bartholomew Alexandra , Werner-Seidler Aliza , Christensen Helen , Batterham Philip J.
Published: June 2024

Background

The COVID-19 pandemic negatively impacted global mental health, with adolescents experiencing disproportionate effects. Limited research has explored the impact of different pandemic restrictions on adolescent mental health, and only a few studies have examined the longer-term impacts of the pandemic on adolescent mental health. These investigations are crucial for informing public health policies, particularly the integration of mental health care in future public health emergencies.

Methods

This study aimed to investigate the impact of lockdown duration and the impact of adolescents’ subjective experiences of the pandemic on their wellbeing, internalising symptoms, and externalising symptoms. Australian adolescents (N = 1,001, mean age = 14.2 years) completed a baseline survey in 2021, shortly after pandemic lockdowns were lifted (Time 1), and a follow-up survey approximately 12 months later (Time 2). Predictors of interest were the total duration of COVID-19 lockdowns across 2020–2021, and adolescents’ subjective experiences of the pandemic on their social connections, learning, technology use and family relationships. A range of covariates were included in analyses to examine subgroup differences.

Results

Linear mixed-effects models indicated that total duration of the lockdown was not associated with any of the outcomes at Time 1 or Time 2 (all ps > 0.017). Negative subjective experience of the pandemic on learning was associated with greater externalising symptoms at both Time 1 (t = 5.17, df = 980, p <.001) and Time 2 (t = 2.72, df = 708, p =.007). Negative subjective experience of the pandemic on social connection was associated with greater internalising symptoms at Time 2 only (t = 3.20, df = 709, p =.001). Negative subjective experience of the pandemic on family relationships or technology use was not associated with any of the outcomes at Time 1 or Time 2 (all ps > 0.017).

Conclusions

Adolescents’ negative subjective experience of the pandemic on learning and social connections was associated with greater internalising and externalising symptoms after the lockdown had been lifted. Duration of lockdowns was not associated with any of the primary outcomes. During future public health emergencies, mental health interventions should be tailored to assist adolescents to adapt to new learning environments, and to build and maintain social connections.
PI3Kγ inhibition combined with DNA vaccination unleashes a B-cell-dependent antitumor immunity that hampers pancreatic cancer
Authors: Curcio Claudia , Mucciolo Gianluca , Roux Cecilia , Brugiapaglia Silvia , Scagliotti Alessandro , Guadagnin Giorgia , Conti Laura , Longo Dario , Grosso Demis , Papotti Mauro Giulio , Hirsch Emilio , Cappello Paola , Varner Judith A. , Novelli Francesco
Published: June 2024

Phosphoinositide-3-kinase γ (PI3Kγ) plays a critical role in pancreatic ductal adenocarcinoma (PDA) by driving the recruitment of myeloid-derived suppressor cells (MDSC) into tumor tissues, leading to tumor growth and metastasis. MDSC also impair the efficacy of immunotherapy. In this study we verify the hypothesis that MDSC targeting, via PI3Kγ inhibition, synergizes with α-enolase (ENO1) DNA vaccination in counteracting tumor growth.

Mice that received ENO1 vaccination followed by PI3Kγ inhibition had significantly smaller tumors compared to those treated with ENO1 alone or the control group, and correlated with i) increased circulating anti-ENO1 specific IgG and IFNγ secretion by T cells, ii) increased tumor infiltration of CD8+ T cells and M1-like macrophages, as well as up-modulation of T cell activation and M1-like related transcripts, iii) decreased infiltration of Treg FoxP3+ T cells, endothelial cells and pericytes, and down-modulation of the stromal compartment and T cell exhaustion gene transcription, iv) reduction of mature and neo-formed vessels, v) increased follicular helper T cell activation and vi) increased “antigen spreading”, as many other tumor-associated antigens were recognized by IgG2c “cytotoxic” antibodies. PDA mouse models genetically devoid of PI3Kγ showed an increased survival and a pattern of transcripts in the tumor area similar to that of pharmacologically-inhibited PI3Kγ-proficient mice. Notably, tumor reduction was abrogated in ENO1 + PI3Kγ inhibition-treated mice in which B cells were depleted.

These data highlight a novel role of PI3Kγ in B cell-dependent immunity, suggesting that PI3Kγ depletion strengthens the anti-tumor response elicited by the ENO1 DNA vaccine.
Recalcitrant intussusception: exploring potential associations with Helicobacter pylori infection - a case report and literature review
Authors: Wang Kuan-Chieh , Chu Chun-Hao , Chiang Che-Ming , Zeng Fu-Ruei , Huang Ching-Wen , Lin Chien-Ming
Published: June 2024

Background

Intussusception, a common cause of abdominal pain in children, often lacks clear underlying causes and is mostly idiopathic. Recurrence, though rare, raises clinical concerns, with rates escalating after each episode. Factors like pathological lead points and Henoch-Schönlein purpura (HSP) are associated with recurrent cases. On the other hand, the prevalence of Helicobacter pylori (H. pylori), often asymptomatic, in children has been declining. Although its infection is reported to be linked with HSP, its role in recurrent intussusception remains unexplored. Further research is needed to understand the interplay among H. pylori (culprit pathogen), HSP (trigger), and intractable intussusception so as to develop effective management strategies.

Case presentation

A two-year-old girl experienced four atypical episodes of intussusception at distinct locations, which later coincided with HSP. Despite treatment with steroids, recurrent intussusception persisted, suggesting that HSP itself was not a major cause for intractable presentations. Subsequent identification of H. pylori infection and treatment with triple therapy resulted in complete resolution of her recalcitrant intussusception.

Conclusion

This instructive case underscored a sequence wherein H. pylori infection triggered HSP, subsequently resulting in recurrent intussusception. While H. pylori infection is not common in young children, the coexistence of intractable intussusception and steroid-resistant recurrent HSP necessitates consideration of H. pylori infection as a potential underlying pathogen.
Bayesian genome-wide TWAS with reference transcriptomic data of brain and blood tissues identified 141 risk genes for Alzheimer’s disease dementia
Authors: Guo Shuyi , Yang Jingjing
Published: June 2024

Background

Transcriptome-wide association study (TWAS) is an influential tool for identifying genes associated with complex diseases whose genetic effects are likely mediated through transcriptome. TWAS utilizes reference genetic and transcriptomic data to estimate effect sizes of genetic variants on gene expression (i.e., effect sizes of a broad sense of expression quantitative trait loci, eQTL). These estimated effect sizes are employed as variant weights in gene-based association tests, facilitating the mapping of risk genes with genome-wide association study (GWAS) data. However, most existing TWAS of Alzheimer's disease (AD) dementia are limited to studying only cis-eQTL proximal to the test gene. To overcome this limitation, we applied the Bayesian Genome-wide TWAS (BGW-TWAS) method to leveraging both cis- and trans- eQTL of brain and blood tissues, in order to enhance mapping risk genes for AD dementia.

Methods

We first applied BGW-TWAS to the Genotype-Tissue Expression (GTEx) V8 dataset to estimate cis- and trans- eQTL effect sizes of the prefrontal cortex, cortex, and whole blood tissues. Estimated eQTL effect sizes were integrated with the summary data of the most recent GWAS of AD dementia to obtain BGW-TWAS (i.e., gene-based association test) p-values of AD dementia per gene per tissue type. Then we used the aggregated Cauchy association test to combine TWAS p-values across three tissues to obtain omnibus TWAS p-values per gene.

Results

We identified 85 significant genes in prefrontal cortex, 82 in cortex, and 76 in whole blood that were significantly associated with AD dementia. By combining BGW-TWAS p-values across these three tissues, we obtained 141 significant risk genes including 34 genes primarily due to trans-eQTL and 35 mapped risk genes in GWAS Catalog. With these 141 significant risk genes, we detected functional clusters comprised of both known mapped GWAS risk genes of AD in GWAS Catalog and our identified TWAS risk genes by protein-protein interaction network analysis, as well as several enriched phenotypes related to AD.

Conclusion

We applied BGW-TWAS and aggregated Cauchy test methods to integrate both cis- and trans- eQTL data of brain and blood tissues with GWAS summary data, identifying 141 TWAS risk genes of AD dementia. These identified risk genes provide novel insights into the underlying biological mechanisms of AD dementia and potential gene targets for therapeutics development.
TORSEL, a 4EBP1-based mTORC1 live-cell sensor, reveals nutrient-sensing targeting by histone deacetylase inhibitors
Authors: Li Canrong , Yi Yuguo , Ouyang Yingyi , Chen Fengzhi , Lu Chuxin , Peng Shujun , Wang Yifan , Chen Xinyu , Yan Xiao , Xu Haolun , Li Shuiming , Feng Lin , Xie Xiaoduo
Published: June 2024

Background

Mammalian or mechanistic target of rapamycin complex 1 (mTORC1) is an effective therapeutic target for diseases such as cancer, diabetes, aging, and neurodegeneration. However, an efficient tool for monitoring mTORC1 inhibition in living cells or tissues is lacking.

Results

We developed a genetically encoded mTORC1 sensor called TORSEL. This sensor changes its fluorescence pattern from diffuse to punctate when 4EBP1 dephosphorylation occurs and interacts with eIF4E. TORSEL can specifically sense the physiological, pharmacological, and genetic inhibition of mTORC1 signaling in living cells and tissues. Importantly, TORSEL is a valuable tool for imaging-based visual screening of mTORC1 inhibitors. Using TORSEL, we identified histone deacetylase inhibitors that selectively block nutrient-sensing signaling to inhibit mTORC1.

Conclusions

TORSEL is a unique living cell sensor that efficiently detects the inhibition of mTORC1 activity, and histone deacetylase inhibitors such as panobinostat target mTORC1 signaling through amino acid sensing.
Exploration of Whisper fine-tuning strategies for low-resource ASR
Authors: Liu Yunpeng , Yang Xukui , Qu Dan
Published: June 2024

Limited data availability remains a significant challenge for Whisper’s low-resource speech recognition performance, falling short of practical application requirements. While previous studies have successfully reduced the recognition error rates of target language speech through fine-tuning, a comprehensive exploration and analysis of Whisper’s fine-tuning capabilities and the advantages and disadvantages of various fine-tuning strategies are still lacking. This paper aims to fill this gap by conducting comprehensive experimental exploration for Whisper’s low-resource speech recognition performance using five fine-tuning strategies with limited supervised data from seven low-resource languages. The results and analysis demonstrate that all fine-tuning strategies explored in this paper significantly enhance Whisper’s performance. However, different strategies vary in their suitability and practical effectiveness, highlighting the need for careful selection based on specific use cases and resources available.
The diagnosis and management of multiple ground-glass nodules in the lung
Authors: Li Quanqing , Xiao Tianjiao , Li Jindong , Niu Yan , Zhang Guangxin
Published: June 2024

The prevalence of low-dose CT (LDCT) in lung cancer screening has gradually increased, and more and more lung ground glass nodules (GGNs) have been detected. So far, a consensus has been reached on the treatment of single pulmonary ground glass nodules, and there have been many guidelines that can be widely accepted. However, at present, more than half of the patients have more than one nodule when pulmonary ground glass nodules are found, which means that different treatment methods for nodules may have different effects on the prognosis or quality of life of patients. This article reviews the research progress in the diagnosis and treatment strategies of pulmonary multiple lesions manifested as GGNs.
Effects of grain intervention on hypothalamic function and the metabolome of blood and milk in dairy cows
Authors: Lin Limei , Guo Kaizhen , Ma Huiting , Zhang Jiyou , Lai Zheng , Zhu Weiyun , Mao Shengyong
Published: June 2024

Background

The hypothalamus plays a crucial role in the health and productivity of dairy cows, yet studies on its functionality and its impact on peripheral circulation in these animals are relatively scarce, particularly regarding dietary interventions. Therefore, our study undertook a comprehensive analysis, incorporating both metabolomics and transcriptomics, to explore the effects of a grain-based diet on the functionality of the hypothalamus, as well as on blood and milk in dairy cows.

Results

The hypothalamic metabolome analysis revealed a significant reduction in prostaglandin E2 (PGE2) level as a prominent response to the grain-based diet introduction. Furthermore, the hypothalamic transcriptome profiling showed a notable upregulation in amino acid metabolism due to the grain-based diet. Conversely, the grain-based diet led to the downregulation of genes involved in the metabolic pathway from lecithin to PGE2, including phospholipase A2 (PLA2G4E, PLA2G2A, and PLA2G12B), cyclooxygenase-2 (COX2), and prostaglandin E synthase (PTGES). Additionally, the plasma metabolome analysis indicated a substantial decrease in the level of PGE2, along with a decline in adrenal steroid hormones (tetrahydrocortisol and pregnenolone) following the grain-based diet introduction. Analysis of the milk metabolome showed that the grain-based diet significantly increased uric acid level while notably decreasing PGE2 level. Importantly, PGE2 was identified as a critical metabolic marker in the hypothalamus, blood, and milk in response to grain intervention. Correlation analysis demonstrated a significant correlation among metabolic alterations in the hypothalamus, blood, and milk following the grain-based diet.

Conclusions

Our findings suggest a potential link between hypothalamic changes and alterations in peripheral circulation resulting from the introduction of a grain-based diet.
The effect of social support and resource support on emotional exhaustion, insomnia, and suicidal ideation among allied health trainees and post-graduate year doctors in Taiwan
Authors: Huang Po-Ching , Lin Chung-Ying , Huang Ru-Yi , Chen Jung-Sheng , Griffiths Mark D. , Strong Carol , Wang Hsiao-Wen , Chen Chiung-Yu , Ko Nai-Ying , Shieh Shyh-Jou
Published: June 2024

Background

COVID-19-related stigmatization refers to COVID-19-related judgements by others that devalue the individual. Such stigmatization towards healthcare workers may cause psychological burden and negative consequences. Such stigmatization may have particularly overwhelmed allied health trainees (AHTs) and post-graduate year doctors (PGYDs) because they just started their medical career. Social support and resource support have been reported to benefit psychological health and reduce stigmatization. Therefore, the present study used a cross-sectional study design to investigate the association between perceived stigma, self-stigma, psychological distress, and negative outcomes (including emotional exhaustion, insomnia and suicidal ideation) among AHTs and PGYDs in Taiwan.

Methods

An online survey distributed between July and December, 2022 received 522 responses. Variables were assessed using the 21-item Depression, Anxiety and Stress Scale, Insomnia Severity Index and a series of self-designed questions to assess social support, resource support, perceived stigma, self-stigma, emotional exhaustion, and suicidal ideation.

Results

Structural equation modeling showed that perceived stigma was associated with self-stigma (standardized coefficient [β] = 0.428, p < 0.001), and self-stigma was associated with psychological distress (β = 0.197, p < 0.001), as well as being associated with emotional exhaustion, insomnia, and suicidal ideation (β = 0.349, 0.556 and 0.212, all p-values < 0.001). While social support and resource support were negatively associated with perceived stigma (β= − 0.175 and − 0.152, p < 0.01), additional associations were found between social support and emotional exhaustion (β= − 0.093, p < 0.001), as well as between resource support and insomnia (β= − 0.120, p < 0.001).

Conclusions

The results showed that COVID-19 related stigmatization was correlated to the detrimental consequences of emotional exhaustion, insomnia and suicidal ideation. Clear paths regarding the associations of social support and resource support with the three negative associations were found as the possible solutions. Strategies to reduce the stigmatization and these negative outcomes, or improve the psychological health will benefit AHTs and PGYDs in maintaining a healthy mental status.
Investigating the relationship between personality traits of hardiness and perfectionism with stress and psychosomatic symptoms: a cross-sectional study among nurses in Iran
Authors: Abdolkarimi Mandana , Sadeghi-Yarandi Mohsen , Sakari Parisa
Published: June 2024

Background

Medical and health sector employees are always exposed to physical and psychological risk factors, which affects their personal, social and professional performance. It’s important to explores the intricate interplay between personality traits, stress levels, and psychosomatic symptoms among nurses as one of the most sensitive jobs in society. Therefore, the present study aimed to investigating the relationship between the personality traits of hardiness and perfectionism with stress and psychosomatic symptoms among nurses.

Methods

This cross-sectional study was conducted among 340 nurses in Mazandaran, Iran in 2022–2023. The instruments utilized to collect data included four questionnaires, namely Cubasa Hardiness Questionnaire, Tehran Multidimensional Perfectionism Questionnaire, Nursing Stress Questionnaire and Takata and Sakata Psychosomatic Questionnaire. The structural equations modeling was used for path analysis. All analyzes were done using SPSS V.25.0 and AMOS V.24.0 software.

Results

The results of the present study revealed that the prevalence of psychosomatic symptoms and stress in nurses was high, and all path coefficients were significant, except for the paths of commitment to stress, challenge to psychosomatic symptoms, self-orientation to psychosomatic symptoms, and community-orientation to psychosomatic symptoms. The results showed that in the final model, the highest coefficient (0.807) is assigned to the other-oriented perfectionism path to psychosomatic symptoms. The weakest coefficient (-0.276) is related to the path of the hardiness component of the challenge to stress. The current research examined the fitting of the proposed model and the suitability of the proposed model was confirmed.

Conclusion

The results of the present study revealed that psychological factors such as personality traits of hardiness, and perfectionism are among the important and influencing parameters on occupational stress, and psychosomatic symptoms and as a result the efficiency and effectiveness of nurses in working environments. Therefore, it is absolutely necessary to implement mitigating and control measures to reduce the mentioned risk factors among nurses in medical settings.
The impact of hypovolemia and PEEP on recirculation in venovenous ECMO: an experimental porcine model
Authors: Antonsen Lars Prag , Espinoza Andreas , Halvorsen Per Steinar , Schalit Itai , Bergan Harald , Lilja Didrik , Landsverk Svein Aslak
Published: June 2024

Background

Recirculation is a common problem in venovenous extracorporeal membrane oxygenation (VV ECMO) and may limit the effect of ECMO treatment due to less efficient blood oxygenation or unfavorable ECMO and ventilator settings. The impact of hypovolemia and positive end expiratory pressure (PEEP) on recirculation is unclear and poorly described in guidelines, despite clinical importance. The aim of this study was to investigate how hypovolemia, autotransfusion and PEEP affect recirculation in comparison to ECMO cannula distance and circuit flow.

Methods

In anesthetized and mechanically ventilated pigs (n = 6) on VV ECMO, we measured recirculation fraction (RF), changes in recirculation fraction (∆RF), hemodynamics and ECMO circuit pressures during alterations in PEEP (5 cmH2O vs 15 cmH2O), ECMO flow (3.5 L/min vs 5.0 L/min), cannula distance (10–14 cm vs 20–26 cm intravascular distance), hypovolemia (1000 mL blood loss) and autotransfusion (1000 mL blood transfusion).

Results

Recirculation increased during hypovolemia (median ∆RF 43%), high PEEP (∆RF 28% and 12% with long and short cannula distance, respectively), high ECMO flow (∆RF 49% and 28% with long and short cannula distance, respectively) and with short cannula distance (∆RF 16%). Recirculation decreased after autotransfusion (∆RF − 45%).

Conclusions

In the present animal study, hypovolemia, PEEP and autotransfusion were important determinants of recirculation. The alterations were comparable to other well-known factors, such as ECMO circuit flow and intravascular cannula distance. Interestingly, hypovolemia increased recirculation without significant change in ECMO drainage pressure, whereas high PEEP increased recirculation with less negative ECMO drainage pressure. Autotransfusion decreased recirculation. The findings are interesting for clinical studies.
The current insights of mitochondrial hormesis in the occurrence and treatment of bone and cartilage degeneration
Authors: Da Wacili , Chen Quan , Shen Bin
Published: June 2024

It is widely acknowledged that aging, mitochondrial dysfunction, and cellular phenotypic abnormalities are intricately associated with the degeneration of bone and cartilage. Consequently, gaining a comprehensive understanding of the regulatory patterns governing mitochondrial function and its underlying mechanisms holds promise for mitigating the progression of osteoarthritis, intervertebral disc degeneration, and osteoporosis. Mitochondrial hormesis, referred to as mitohormesis, represents a cellular adaptive stress response mechanism wherein mitochondria restore homeostasis and augment resistance capabilities against stimuli by generating reactive oxygen species (ROS), orchestrating unfolded protein reactions (UPRmt), inducing mitochondrial-derived peptides (MDP), instigating mitochondrial dynamic changes, and activating mitophagy, all prompted by low doses of stressors. The varying nature, intensity, and duration of stimulus sources elicit divergent degrees of mitochondrial stress responses, subsequently activating one or more signaling pathways to initiate mitohormesis. This review focuses specifically on the effector molecules and regulatory networks associated with mitohormesis, while also scrutinizing extant mechanisms of mitochondrial dysfunction contributing to bone and cartilage degeneration through oxidative stress damage. Additionally, it underscores the potential of mechanical stimulation, intermittent dietary restrictions, hypoxic preconditioning, and low-dose toxic compounds to trigger mitohormesis, thereby alleviating bone and cartilage degeneration.
Efficacy of RCI001 as a therapeutic candidate of dry eye disease in a modified mixed dry eye model
Authors: Jung Young-ho , Ku Young Ah , Moon Jayoon , Kim Seunghoon , Ryu Jin Suk , Yoon Chang Ho , Chung Myung Hee , Kim Yong Ho , Kim Mee Kum , Kim Dong Hyun
Published: June 2024

Background

To evaluate the therapeutic effects of topical RCI001 (RCI) and compare its efficacy with that of 1% prednisolone acetate (PDE) and 5% Lifitegrast in a modified mixed dry eye disease (DED) model.

Methods

The environmental DED model was induced in BALB/c mice in a dry chamber with scopolamine. The eyes of the mice were treated topically with phosphate buffered saline (PBS), PDE, Lifitegrast or RCI twice daily for 1 week. Ocular surface staining (OSS), tear secretion, inflammatory cytokines in the ocular surface and lacrimal gland, and immunofluorescence staining in the conjunctiva and cornea(CC) were assessed.

Results

The RCI group demonstrated better improvement of OSS and tear secretion than the PBS group (OSS, PBS: 13.0 ± 1.6, RCI: 9.4 ± 3.0; tear secretion, PBS: 5.0 ± 0.4 mm, RCI: 7.0 ± 0.3 mm, each P < 0.001) and better clinical efficacy than PDE and Lifitegrast groups on Day 7 (improvement rate of OSS, RCI: 32.45%, Lifitegrast: 13.13%, PDE: 12.25%). The RCI group resulted in significantly lower expression of oxidative stress markers in the CC than the PBS group (4-HNE, NOX2, and NOX4 in the conjunctiva; NOX2 in the cornea, each P < 0.05). However, the PDE and Lifitegrast groups did not show significant differences compared with the PBS group. There were no significant differences of inflammatory cytokines in the ocular surface and lacrimal gland between all groups.

Conclusion

Topical RCI001 showed excellent therapeutic effects in environmental DED models by stimulating tear secretion, modulating oxidative stress and improving corneal epithelial healing compared to 1% PDE and 5% Lifitegrast.
Tetanus– a case report highlighting the challenges in diagnosis and treatment
Authors: Boer Menno , de Voogd Martijn , Niemeijer Nicolasine Diana , van Hoeven Lonneke
Published: June 2024

Tetanus has become an increasingly rare infectious disease due to the development of successful vaccination programs in the mid-20th century. In resource-rich countries, mainly unvaccinated or partly vaccinated risk groups are affected, whereas tetanus still remains prevalent in resource-limited countries. The decreasing incidence in developed countries has hindered clinical trials evaluating the best treatment modalities for tetanus infections. Current guidelines are based on a small number of studies and case reports. So far, these studies have shown potential benefits of treating tetanus infections with benzodiazepines, magnesium sulfate and baclofen. Additionally, several treatments have been shown to be useful in stabilizing and supporting patients with tetanus. However, each treatment modality has limitations, from negative side effects to logistical challenges, especially in developing countries. Therefore, further knowledge is required to evaluate the best use of each treatment and to further optimize patient care. This knowledge can contribute to the reduction of the burden of disease in countries where tetanus remains prevalent and where resources are limited, though vaccination is the most effective method to achieve this. This case report describes the treatment of a Dutch patient with tetanus infection and illustrates the role of benzodiazepines as well as other key aspects of treating patients with tetanus.
A handheld device for intra-cavity and ex vivo fluorescence imaging of breast conserving surgery margins with 5-aminolevulinic acid
Authors: Gibson Christopher , Wang Shirley C. , Phoon Arcturus , Thalanki Anantha Nayana , Ottolino-Perry Kathryn , Petropoulos Stephen , Qureshi Zuha , Subramanian Vasanth , Shahid Anam , O’Brien Cristiana , Carcone Steven , Chung Suzanne , Tsui Teresa , Son Viktor , Sukhram Mayleen , Meng Fannong , Done Susan J. , Easson Alexandra M. , Cil Tulin , Reedijk Michael , Leong Wey L. , DaCosta Ralph S.
Published: June 2024

Background

Visualization of cancer during breast conserving surgery (BCS) remains challenging; the BCS reoperation rate is reported to be 20-70% of patients. An urgent clinical need exists for real-time intraoperative visualization of breast carcinomas during BCS. We previously demonstrated the ability of a prototype imaging device to identify breast carcinoma in excised surgical specimens following 5-aminolevulinic acid (5-ALA) administration. However, this prototype device was not designed to image the surgical cavity for remaining carcinoma after the excised lumpectomy specimen is removed. A new handheld fluorescence (FL) imaging prototype device, designed to image both excised specimens and within the surgical cavity, was assessed in a clinical trial to evaluate its clinical utility for first-in-human, real-time intraoperative imaging during index BCS.

Results

The imaging device combines consumer-grade imaging sensory technology with miniature light-emitting diodes (LEDs) and multiband optical filtering to capture high-resolution white light (WL) and FL digital images and videos. The technology allows for visualization of protoporphyrin IX (PpIX), which fluoresces red when excited by violet-blue light. To date, $$n = 17$$

n
=
17

patients have received $$20\frac{\text {mg}}{\textrm{kg}}$$

20

mg
kg

bodyweight (BW) 5-ALA orally 2-4 h before imaging to facilitate the accumulation of PpIX within tumour cells. Tissue types were identified based on their colour appearance. Breast tumours in sectioned lumpectomies appeared red, which contrasted against the green connective tissues and orange-brown adipose tissues. In addition, ductal carcinoma in situ (DCIS) that was missed during intraoperative standard of care was identified at the surgical margin at <1 mm depth. In addition, artifacts due to the surgical drape, illumination, and blood within the surgical cavity were discovered.

Conclusions

This study has demonstrated the detection of a grossly occult positive margin intraoperatively. Artifacts from imaging within the surgical cavity have been identified, and potential mitigations have been proposed.

Trial Registration

Identifier: (Trial start date is September 2010. It was registered to ClinicalTrials.gov retrospectively on April 23, 2013, then later updated on April 9, 2020, to reflect the introduction of the new imaging device.)
A review of cell-type specific circuit mechanisms underlying epilepsy
Authors: Zhao Peilin , Ding Xiaomi , Li Lini , Jiang Guohui
Published: June 2024

Epilepsy is a prevalent neurological disorder, yet its underlying mechanisms remain incompletely understood. Accumulated studies have indicated that epilepsy is characterized by abnormal neural circuits. Understanding the circuit mechanisms is crucial for comprehending the pathogenesis of epilepsy. With advances in tracing and modulating tools for neural circuits, some epileptic circuits have been uncovered. This comprehensive review focuses on the circuit mechanisms underlying epilepsy in various neuronal subtypes, elucidating their distinct roles. Epileptic seizures are primarily characterized by the hyperactivity of glutamatergic neurons and inhibition of GABAergic neurons. However, specific activated GABAergic neurons and suppressed glutamatergic neurons exacerbate epilepsy through preferentially regulating the activity of GABAergic neurons within epileptic circuits. Distinct subtypes of GABAergic neurons contribute differently to epileptic activities, potentially due to their diverse connection patterns. Moreover, identical GABAergic neurons may assume distinct roles in different stages of epilepsy. Both GABAergic neurons and glutamatergic neurons with long-range projecting fibers innervate multiple nuclei; nevertheless, not all of these circuits contribute to epileptic activities. Epileptic circuits originating from the same nuclei may display diverse contributions to epileptic activities, and certain glutamatergic circuits from the same nuclei may even exert opposing effects on epilepsy. Neuromodulatory neurons, including cholinergic, serotonergic, dopaminergic, and noradrenergic neurons, are also implicated in epilepsy, although the underlying circuit mechanisms remain poorly understood. These studies suggest that epileptic nuclei establish intricate connections through cell-type-specific circuits and play pivotal roles in epilepsy. However, there are still limitations in knowledge and methods, and further understanding of epileptic circuits is crucial, particularly in the context of refractory epilepsy.