bluuebunny/crossref_metadata_2025 huggingface dataset:
Leucine supplementation in maternal high-fat diet alleviated adiposity and glucose intolerance of adult mice offspring fed a postweaning high-fat diet
Authors: Kim Juhae , Kim Juyoung , Kwon Young Hye
Published: April 2023

Background

Combined maternal and postnatal high-fat (HF) diet intake predisposes offspring to metabolic dysregulation during adulthood. As the inhibitory effects of leucine consumption on obesity and metabolic disorders have been reported, the effects of maternal leucine supplementation on metabolic dysregulation in adult offspring were investigated.

Methods

Female mice were exposed to a control (C) or HF diet, with or without leucine (L) supplementation (1.5%, w/v), 3 weeks before mating, during pregnancy, and during lactation (C, CL, HF, and HFL). Male offspring were exposed to an HF diet for 12 weeks after weaning (C/HF, CL/HF, HF/HF, and HFL/HF). Serum biochemical parameters were determined for both the dams and offspring. Oral glucose tolerance test and qRT-PCR analysis were used to investigate metabolic dysregulation in the offspring.

Results

HFL dams exhibited higher relative adipose tissue weights than HF dams. Body weight, relative adipose tissue weight, and serum glucose levels were lower in the HFL/HF offspring than in the HF/HF offspring. Maternal leucine supplementation tended to alleviate glucose intolerance in the offspring of HF diet-fed dams. Additionally, mRNA levels of fibroblast growth factor 21 (FGF21), a hepatokine associated with glucose homeostasis, were higher in HFL/HF offspring than in HF/HF offspring and were negatively correlated with adiposity and serum glucose levels. The mRNA levels of genes encoding a FGF21 receptor complex, Fgf receptor 1 and klotho β, and its downstream targets, proliferator‐activated receptor‐γ co‐activator 1α and sirtuin 1, were higher in adipose tissues of the HFL/HF offspring than in those of the HF/HF offspring. Serum lipid peroxide levels were lower in HFL dams than in HF dams and positively correlated with body and adipose tissue weights of offspring.

Conclusions

Leucine supplementation in HF diet-fed dams, but not in control diet-fed dams, resulted in an anti-obesity phenotype accompanied by glucose homeostasis in male offspring challenged with postnatal HF feeding. Activation of FGF21 signaling in the adipose tissue of offspring may be responsible for these beneficial effects of leucine.
Compensatory remodeling of a septo-hippocampal GABAergic network in the triple transgenic Alzheimer’s mouse model
Authors: Wander Connor M , Li Ya-Dong , Bao Hechen , Asrican Brent , Luo Yan-Jia , Sullivan Heather A , Chao Tzu-Hao Harry , Zhang Wei-Ting , Chéry Samantha L , Tart Dalton S , Chen Ze-Ka , Shih Yen-Yu Ian , Wickersham Ian R , Cohen Todd J , Song Juan
Published: April 2023

Background

Alzheimer’s disease (AD) is characterized by a progressive loss of memory that cannot be efficiently managed by currently available AD therapeutics. So far, most treatments for AD that have the potential to improve memory target neural circuits to protect their integrity. However, the vulnerable neural circuits and their dynamic remodeling during AD progression remain largely undefined.

Methods

Circuit-based approaches, including anterograde and retrograde tracing, slice electrophysiology, and fiber photometry, were used to investigate the dynamic structural and functional remodeling of a GABAergic circuit projected from the medial septum (MS) to the dentate gyrus (DG) in 3xTg-AD mice during AD progression.

Results

We identified a long-distance GABAergic circuit that couples highly connected MS and DG GABAergic neurons during spatial memory encoding. Furthermore, we found hyperactivity of DG interneurons during early AD, which persisted into late AD stages. Interestingly, MS GABAergic projections developed a series of adaptive strategies to combat DG interneuron hyperactivity. During early-stage AD, MS-DG GABAergic projections exhibit increased inhibitory synaptic strength onto DG interneurons to inhibit their activities. During late-stage AD, MS-DG GABAergic projections form higher anatomical connectivity with DG interneurons and exhibit aberrant outgrowth to increase the inhibition onto DG interneurons.

Conclusion

We report the structural and functional remodeling of the MS-DG GABAergic circuit during disease progression in 3xTg-AD mice. Dynamic MS-DG GABAergic circuit remodeling represents a compensatory mechanism to combat DG interneuron hyperactivity induced by reduced GABA transmission.
The relationship between carbonic anhydrase IX (CAIX) and patient survival in breast cancer: systematic review and meta-analysis
Authors: Shamis Suad A. K. , Edwards Joanne , McMillan Donald C.
Published: April 2023

Purpose

Hypoxia is a characteristic of many solid tumours and an adverse prognostic factor for cancer therapy. Hypoxia results in upregulation of carbonic anhydrase IX (CAIX) expression, a pH-regulating enzyme. Many human tissue studies have examined the prognostic value of CAIX expression in breast cancer but have yielded inconsistent results. Therefore, a systematic review and meta-analysis was undertaken to assess the prognostic value of CAIX expression for breast cancer patients.

Methods

The electronic databases were systematically searched to identify relevant papers. The clinical outcomes included disease-free survival (DFS), recurrence-free survival (RFS) and overall survival (OS) in breast cancer patients. Review Manager version 5.4 was employed to analysis data from 23 eligible studies (containing 8390 patients).

Results

High CAIX expression was associated with poorer RFS [HR = 1.42, 95% CI (1.32−1.51), p < 0.00001], DFS [HR = 1.64, 95% CI (1.34−2.00), p < 0.00001], and OS [HR = 1.48, 95% CI (1.22−1.80), p < 0.0001]. Heterogeneity was observed across the studies. There was an effect of the CAIX antibody employed, scoring methods, and tumour localisation on CAIX expression.

Conclusion

CAIX overexpression was significantly associated with poorer RFS, DFS, and OS in breast cancer patients. However, further work in high quantity tissue cohorts is required to define the optimal methodological approach.
Improving breastfeeding support through the implementation of the Baby-Friendly Hospital and Community Initiatives: a scoping review
Authors: Walsh Aisling , Pieterse Pieternella , Mishra Nita , Chirwa Ellen , Chikalipo Maria , Msowoya Chimwemwe , Keating Ciara , Matthews Anne
Published: April 2023

Background

Improved breastfeeding practices have the potential to save the lives of over 823,000 children under 5 years old globally every year. The Baby-Friendly Hospital Initiative (BFHI) is a global campaign by the World Health Organization and the United Nations Children’s Fund, which promotes best practice to support breastfeeding in maternity services. The Baby-Friendly Community Initiative (BFCI) grew out of step 10, with a focus on community-based implementation. The aim of this scoping review is to map and examine the evidence relating to the implementation of BFHI and BFCI globally.

Methods

This scoping review was conducted according to the Joanna Briggs Institute methodology for scoping reviews. Inclusion criteria followed the Population, Concepts, Contexts approach. All articles were screened by two reviewers, using Covidence software. Data were charted according to: country, study design, setting, study population, BFHI steps, study aim and objectives, description of intervention, summary of results, barriers and enablers to implementation, evidence gaps, and recommendations. Qualitative and quantitative descriptive analyses were undertaken.

Results

A total of 278 articles were included in the review. Patterns identified were: i) national policy and health systems: effective and visible national leadership is needed, demonstrated with legislation, funding and policy; ii) hospital policy is crucial, especially in becoming breastfeeding friendly and neonatal care settings iii) implementation of specific steps; iv) the BFCI is implemented in only a few countries and government resources are needed to scale it; v) health worker breastfeeding knowledge and training needs strengthening to ensure long term changes in practice; vi) educational programmes for pregnant and postpartum women are essential for sustained exclusive breastfeeding. Evidence gaps include study design issues and need to improve the quality of breastfeeding data and to perform prevalence and longitudinal studies.

Conclusion

At a national level, political support for BFHI implementation supports expansion of Baby-Friendly Hospitals. Ongoing quality assurance is essential, as is systematic (re)assessment of BFHI designated hospitals. Baby Friendly Hospitals should provide breastfeeding support that favours long-term healthcare relationships across the perinatal period. These results can help to support and further enable the effective implementation of BFHI and BFCI globally.
Treatment outcomes of stereotactic body radiation therapy for pulmonary metastasis from sarcoma: a multicenter, retrospective study
Authors: Lee Tae Hoon , Kim Hak Jae , Kim Jin Ho , Kim Mi-Sook , Jang Won Il , Kim Eunji , Kim Kyung Su
Published: April 2023

Purpose

The aim of this study was to evaluate the treatment outcomes and potential dose-response relationship of stereotactic body radiation therapy (SBRT) for pulmonary metastasis of sarcoma.

Materials and methods

A retrospective review of 39 patients and 71 lesions treated with SBRT from two institutions was performed. The patients had oligometastatic or oligoprogressive disease, or were receiving palliation. Doses of 20–60 Gy were delivered in 1–5 fractions. The local control per tumor (LCpT) was evaluated according to the biologically effective dose with an α/β ratio of 10 (BED10) of the prescribed dose (BED10 ≥ 100 Gy vs. BED10 < 100 Gy). Clinical outcomes per patient, including local control per patient (LCpP), pulmonary progression-free rate (PPFR), any progression-free rate (APFR), and overall survival (OS) were investigated.

Results

The median follow-up period was 27.2 months. The 1-, 2-, and 3-year LCpT rates for the entire cohort were 100.0%, 88.3%, and 73.6%, respectively. There was no observed difference in LCpT between the two BED10groups (p = 0.180). The 3-year LCpP, PPFR, APFR, and OS rates were 78.1%, 22.7%, 12.9%, and 83.7%, respectively. Five (12.8%) patients with oligometastasis had long-term disease-free intervals, with a median survival period of 40.7 months. Factors that were associated with a worse prognosis were oligoprogression (vs. oligometastasis), multiple pulmonary metastases, and simultaneous extrathoracic metastasis.

Conclusion

SBRT for pulmonary metastasis of sarcoma is effective. Some selected patients may achieve durable response. Considerations of SBRT indication and disease extent may be needed as they may influence the prognosis.
Research hotspots and trends of microRNAs in intervertebral disc degeneration: a comprehensive bibliometric analysis
Authors: Chen Shuang , Wang Yi , Wu Huanxi , Fang Xiaoyang , Wang Chenyu , Wang Nan , Xie Lin
Published: April 2023

Background

MicroRNAs (miRNAs) are involved in various pathological processes, such as proliferation, growth, and apoptosis, of intervertebral disc (IVD) cells and play an important role in the development of intervertebral disc degeneration (IDD). Although some studies have reported the role of miRNAs in IDD, scientific econometric analysis in this field is not available.

Objectives

We designed this study to describe the current research trends and potential mechanisms associated with the role of miRNAs in IDD and to provide new ideas for future research in this field.

Methods

We conducted a bibliometric analysis of the publications on the role of miRNAs in IDD included in the Web of Science core collection database to elucidate the current research trends in this field. The potential mechanisms were constructed using the Arrowsmith project.

Results

We found that the number of miRNAs and IDD-related publications increased over the years. China was the most important contributor to research in this field. The top three institutions in terms of number of articles published were Huazhong University of Science and Technology, Shanghai Jiao Tong University, and Xi’an Jiao Tong University. Shanghai Jiao Tong University had the highest number of citations. Experimental and thermal medicine had the maximum number of documents, and Cell promotion had the most citations. The journal with the most mean times cited per study was Annals of the Rheumatic Diseases. The author Wang K had the highest number of publications, and Wang HQ had the highest number of citations. These two authors made important contributions to the research in this field. The keyword analysis showed that recent studies have focused on miRNAs regulating nucleus pulposus cell apoptosis and proliferation. Moreover, we revealed the potential mechanisms of miRNAs associated with IDD, including miRNAs regulating the extracellular matrix (ECM) degradation, mediating cartilage endplate (CEP) degeneration, and participating in inflammatory responses.

Conclusion

We demonstrated the knowledge map of miRNAs and IDD-related research through bibliometric analysis and elucidated the current research status and hotspots in this field. The mechanisms by which miRNAs regulate the apoptosis and proliferation of degenerated IVDs, promote ECM degradation, mediate CEP degeneration, and participate in inflammatory responses should be explored in further studies.
Behavioral and emotional difficulties and HIV treatment outcomes among HIV-infected children in rural southwestern China
Authors: Zhou Yesheng , Tang Kailing , Lu Hongyan , Chen Hongli , Xie Haomin , Li Zeyu , Huang Jinghua , Fang Ningye , Chen Siya , Wang Hong , He Qin , Chen Huanhuan , Liu Xiu , Lan Guanghua , Zhu Qiuying , Chen Yi , Zhang Xiangjun , Ruan Yuhua , Liang Shujia
Published: April 2023

Background

Previous studies have not clearly demonstrated the impact of behavioral and emotional problems (BEDs) on treatment outcomes among HIV-infected children on antiretroviral therapy (ART). This study aimed to describe the prevalence of BEDs among this population and identify the factors associated with HIV treatment outcomes.

Methods

This cross-sectional study was conducted in Guangxi, China, between July and August 2021. HIV-infected children answered questionnaires about BEDs, physical health, social support, and whether they have missed doses in the past month. BEDs were assessed using the Chinese version of the self-reported Strengths and Difficulties Questionnaire (SDQ-C). The self-reported survey data were linked to participants’ HIV care information that was obtained from the national surveillance database. Univariate and multivariate logistic regression models were used to identify factors that were associated with missed doses in the past month and virological failure.

Results

The study sample was 325 HIV-infected children. HIV-infected children had a higher proportion of abnormal scores on SDQ-C total difficulties compared to their peers in the general population (16.9 vs 10.0%; P = 0.002). An abnormal SDQ-C total difficulties score (AOR = 2.06, 95%CI: 1.10–3.88) and infrequency of receiving assistance and support from parents over the past 3 months (AOR = 1.85, 95%CI: 1.12–3.06) were significantly associated with missed doses in the past month. Between the ages of 14–17 years (AOR = 2.66, 95% CI: 1.37–5.16), female (AOR = 2.21, 95% CI: 1.20–4.08), and suboptimal adherence (AOR = 2.45, 95% CI: 1.32–4.57) were significantly associated with virological failure.

Conclusions

Children’s mental health plays a role in HIV treatment outcomes. Psychological interventions should be promoted in pediatric HIV care clinics to improve children’s mental health status and HIV treatment outcomes.
Notch signaling is activated in knee-innervating dorsal root ganglia in experimental models of osteoarthritis joint pain
Authors: Wang Lai , Ishihara Shingo , Li Jun , Miller Rachel E. , Malfait Anne-Marie
Published: April 2023

Background

We aimed to explore activation of the Notch signaling pathway in knee-innervating lumbar dorsal root ganglia (DRG) in the course of experimental osteoarthritis (OA) in mice, and its role in knee hyperalgesia.

Methods

Cultured DRG cells were stimulated with the TLR4 agonist, lipopolysaccharide (LPS). Notch signaling in the cells was either inhibited with the γ-secretase inhibitor, DAPT, or with soluble Jagged1, or activated through immobilized Jagged1. CCL2 production was analyzed at mRNA and protein levels. In in vivo experiments, knee hyperalgesia was induced in naïve mice through intra-articular (IA) injection of LPS. The effect of inhibiting Notch signaling was examined by pre-injecting DAPT one hour before LPS. OA was induced through surgical destabilization of the medial meniscus (DMM) in male C57BL/6 mice. Gene expression in DRG was analyzed by qRT-PCR and RNAscope in situ hybridization. Activated Notch protein (NICD) expression in DRG was evaluated by ELISA and immunofluorescence staining. DAPT was injected IA 12 weeks post DMM to inhibit Notch signaling, followed by assessing knee hyperalgesia and CCL2 expression in the DRG.

Results

In DRG cell cultures, LPS increased NICD in neuronal cells. Inhibition of Notch signaling with either DAPT or soluble Jagged1 attenuated LPS-induced increases of Ccl2 mRNA and CCL2 protein. Conversely, activating Notch signaling with immobilized Jagged1 enhanced these LPS effects. In vivo, IA injection of LPS increased expression of Notch genes and NICD in the DRG. Pre-injection of DAPT prior to LPS alleviated LPS-induced knee hyperalgesia, and decreased LPS-induced CCL2 expression in the DRG. Notch signaling genes were differentially expressed in the DRG from late-stage experimental OA. Notch1, Hes1, and NICD were increased in the neuronal cell bodies in DRG after DMM surgery. IA administration of DAPT alleviated knee hyperalgesia post DMM, and decreased CCL2 expression in the DRG.

Conclusions

These findings suggest a synergistic effect of Notch signaling with TLR4 in promoting CCL2 production and mediating knee hyperalgesia. Notch signaling is activated in knee-innervating lumbar DRG in mice with experimental OA, and is involved in mediating knee hyperalgesia. The pathway may therefore be explored as a target for alleviating OA pain.
Steeper memory decline after COVID-19 lockdown measures
Authors: Bakker Els D. , van der Pas Stéphanie L. , Zwan Marissa D. , Gillissen Freek , Bouwman Femke H. , Scheltens Philip , van der Flier Wiesje M. , van Maurik Ingrid S.
Published: April 2023

Background

During COVID-19 lockdown measures, memory clinic patients reported worries for faster cognitive decline, due to loss of structure and feelings of loneliness and depression. We aimed to investigate the impact of the COVID-19 lockdown on rate of cognitive decline in a mixed memory clinic population, compared to matched historical controls.

Methods

We included patients who visited Alzheimer Center Amsterdam 6 months to 1 week before the first Dutch COVID-19 lockdown, and had a second visit 1 year later, after this lockdown period (n = 113; 66 ± 7 years old; 30% female;n = 55 dementia,n = 31 mild cognitive impairment (MCI),n = 18 subjective cognitive decline (SCD),n = 9 postponed diagnosis). Historical controls (visit in 2016/2017 and second visit 1 year later (n = 640)) were matched 1:1 to lockdown patients by optimal Mahalanobis distance matching (both groupsn = 113). Groups were well matched. Differences between lockdown patients and historical controls over time in Mini-Mental State Examination, Trail Making Test part A and B, Rey-Auditory Verbal Learning Test (RAVLT) immediate and delayed recall, and category fluency scores were analyzed using linear mixed effect models with random intercepts. We examined differences in rate of cognitive decline between whole groups, and after stratification in SCD, MCI, and dementia separately.

Results

Lockdown patients had a faster rate of memory decline compared to controls on both RAVLT immediate [B(SE) =  − 2.62 (1.07),p = 0.015] and delayed recall [B(SE) =  − 1.07 (0.34),p = 0.002]. Stratification by syndrome diagnosis showed that this effect was largely attributable to non-demented participants, as we observed faster memory decline during lockdown in SCD and MCI (RAVLT immediate [SCD:B(SE) =  − 6.85 (2.97),p = 0.027; MCI:B(SE) =  − 6.14 (1.78),p = 0.001] and delayed recall [SCD:B(SE) =  − 2.45 (1.11),p = 0.035; MCI:B(SE) =  − 1.50 (0.51),p = 0.005]), but not in dementia.

Conclusion

Memory clinic patients, specifically in pre-dementia stages, showed faster memory decline during COVID-19 lockdown, providing evidence that lockdown regulations had a deleterious effect on brain health. In individuals that may have been able to deal with accumulating, subclinical neuropathology under normal and structured circumstances, the additional stress of lockdown regulations may have acted as a “second hit,” resulting in less beneficial disease trajectory.
Cribriform adenocarcinoma of the minor salivary glands: a case report
Authors: Chen Tanya , Mamdani Mohammed , Vescan Allan , MacMillan Christina , Davies Joel
Published: April 2023

Background

Polymorphous adenocarcinoma is the third most common malignant salivary gland tumor. Within polymorphous adenocarcinoma, cribriform adenocarcinoma of salivary glands is a rare subtype and resembles papillary thyroid carcinoma histopathologically. Diagnostically, cribriform adenocarcinoma of salivary glands is challenging for pathologists and surgeons alike as initial presentation and cytologic nuclear features can be easily confused with papillary thyroid carcinoma arising from a thyroglossal duct remnant or lingual thyroid.

Case presentation

A healthy 64-year-old Caucasian woman presented to a community otolaryngologist with a 4-year history of progressive postnasal drip, globus sensation, and eventual dysphonia. Flexible fiberoptic laryngoscopy showed a large, smooth, vallecular lesion filling the oropharynx. Computed tomography imaging of the neck showed a rounded heterogeneous mass centered within the right aspect of the oropharynx measuring 4.2 × 4.4 × 4.5 cm. Fine needle aspiration biopsy was suspicious for papillary carcinoma due to microscopic findings of malignant cells, nuclear grooves, and a powdery chromatin pattern. In the operating room, the tumor was resected en bloc using a lateral pharyngotomy approach with partial resection of the right lateral hyoid. A limited cervical lymphadenectomy was performed to facilitate the lateral pharyngotomy approach and two out of three lymph nodes demonstrated regional metastatic disease. Nuclear grooves, nuclear membrane notching, and occasional intranuclear pseudoinclusions were identified, which are overlapping histopathological characteristics of papillary thyroid carcinoma and cribriform adenocarcinoma of salivary glands. It was negative for thyroglobulin and thyroid transcription factor-1, which was in keeping with cribriform adenocarcinoma of salivary glands rather than papillary thyroid carcinoma.

Conclusion

It is difficult to distinguish cribriform adenocarcinoma of salivary glands from papillary thyroid carcinoma solely by cytology, and the distinct characteristics of regional lymph node metastasis coupled with nuanced histologic differences should be emphasized in the evaluation of patients presenting with neck lymphadenopathy and an unknown primary or tongue mass. If sufficient fine needle aspiration biopsy material is available, thyroid transcription factor-1, thyroglobulin, or molecular testing may prove useful in differentiating cribriform adenocarcinoma of salivary glands from papillary thyroid carcinoma. A misdiagnosis of papillary thyroid carcinoma may lead to inappropriate treatment including unnecessary thyroidectomy. Therefore, it is critical for both pathologists and surgeons to be aware of this uncommon entity to avoid misdiagnosis and subsequent mismanagement.
Foodborne botulism and the importance of recognizing the disease in the emergency department: a case report
Authors: De Vet Seppe , Tackaert Thomas , Smet Mike , Raemen Hannelore
Published: April 2023

Background

Botulism is a rare neuroparalytic disease that has only presented itself 19 times in the last 30 years in Belgium. Patients present to emergency services with a wide range of complaints. Foodborne botulism is a forgotten yet life-threatening disease.

Case presentation

We describe a case of a Caucasian female in her 60s that presented to the emergency with reflux with nausea and spasmodic epigastric pain, no vomiting, dry mouth, and weakness in both legs. The symptoms started after ingestion of Atlantic wolffish. After exclusion of other more common causes, foodborne botulism was suspected. The patient was admitted to the intensive care unit for mechanical ventilation. Following treatment with trivalent botulinum antitoxin, she made a full neurologic recovery.

Conclusion

It is important to rapidly recognize the possible diagnosis of botulism even if the neurological symptoms are not dominant. Rapid neurologic dysfunction and respiratory difficulties starts between 6 and 72 hours after ingestion. The decision to administer antitoxins should, however, be based on the presumptive clinical diagnosis and diagnosis should not delay therapy.
ASAP2 interrupts c-MET-CIN85 interaction to sustain HGF/c-MET-induced malignant potentials in hepatocellular carcinoma
Authors: Ma Xiao-Lu , Nie Yan-Yan , Xie Su-Hong , Zheng Hui , Tong Ying , Wang Yan-Chun , Yan Tian-Qing , Meng Xin , Cao Jia-Zhen , Tang Wei-Guo , Guo Lin , Lu Ren-Quan
Published: April 2023

Background

Sustained activation of hepatocyte growth factor (HGF)/c-MET signaling is a major driver of hepatocellular carcinoma (HCC) progression, but underlying mechanism is unclear. ArfGAP With SH3 Domain, Ankyrin Repeat And PH Domain 2 (ASAP2) can reportedly activate GTPases and promote receptor tyrosine kinase signaling. However, the exact role of ASAP2 in HCC, especially for c-MET activation, also remains elusive.

Methods

ASAP2 expression levels in HCC tissues and cells were quantified using qRT-PCR, western blot (WB) analysis, and immunohistochemistry staining. Cell counting kit-8 (CCK-8) and colony formation assays were performed to evaluate cell proliferation rates. Flow cytometry assays were conducted to assess apoptosis rates. Wound healing and Transwell assays were performed to determine cell migration and invasion capacities. Epithelial-mesenchymal transition (EMT)-related marker expression levels were also examined. Subcutaneous implantation and tail vein injection models were applied for in vivo growth and metastasis evaluations, respectively. Bioinformatics analyses of The Cancer Genome Atlas and STRING datasets were performed to explore ASAP2 downstream signaling. Co-immunoprecipitation and Cycloheximide chasing experiments were performed to assess protein–protein interactions and protein half-life, respectively.

Results

ASAP2 had higher expression levels in HCC tissues than in normal liver, and also predicted poor prognosis. Knocking down ASAP2 significantly impaired cell proliferation, migration, and invasion capacities, but promoted apoptosis in HCC cells in vitro. However, overexpression of ASAP2 achieved the opposite effects. In vivo experiments confirmed that ASAP2 could promote HCC cell growth and facilitate lung metastasis. Interestingly, ASAP2 was essential for triggering EMT. Gene Set Enrichment Analysis demonstrated that c-MET signaling was greatly enriched in ASAP2-high HCC cases. Additionally, c-MET signaling activity was significantly decreased following ASAP knockdown, evidenced by reduced c-MET, p-AKT, and p-ERK1/2 protein levels. Importantly, ASAP2 knockdown effectively attenuated HGF/c-MET signaling-induced malignant phenotypes. c-MET and ASAP2 expression levels were positively correlated in our cohort. Mechanistically, ASAP2 can directly bind to CIN85, thereby disrupting its interaction with c-MET, and can thus antagonize CIN85-induced c-MET internalization and lysosome-mediated degradation. Notably, knocking down CIN85 can rescue the observed inhibitory effects caused by ASAP2 knockdown.

Conclusions

This study highlights the importance of ASAP2 in sustaining c-MET signaling, which can facilitate HCC progression.
Perinatal origins of bronchopulmonary dysplasia—deciphering normal and impaired lung development cell by cell
Authors: Mižíková I. , Thébaud B.
Published: April 2023

Bronchopulmonary dysplasia (BPD) is a multifactorial disease occurring as a consequence of premature birth, as well as antenatal and postnatal injury to the developing lung. BPD morbidity and severity depend on a complex interplay between prenatal and postnatal inflammation, mechanical ventilation, and oxygen therapy as well as associated prematurity-related complications. These initial hits result in ill-explored aberrant immune and reparative response, activation of pro-fibrotic and anti-angiogenic factors, which further perpetuate the injury. Histologically, the disease presents primarily by impaired lung development and an arrest in lung microvascular maturation. Consequently, BPD leads to respiratory complications beyond the neonatal period and may result in premature aging of the lung. While the numerous prenatal and postnatal stimuli contributing to BPD pathogenesis are relatively well known, the specific cell populations driving the injury, as well as underlying mechanisms are still not well understood. Recently, an effort to gain a more detailed insight into the cellular composition of the developing lung and its progenitor populations has unfold. Here, we provide an overview of the current knowledge regarding perinatal origin of BPD and discuss underlying mechanisms, as well as novel approaches to study the perturbed lung development.
Physics-informed deep learning framework to model intense precipitation events at super resolution
Authors: Teufel B. , Carmo F. , Sushama L. , Sun L. , Khaliq M. N. , Bélair S. , Shamseldin A. , Kumar D. Nagesh , Vaze J.
Published: April 2023

Physical modeling of precipitation at fine (sub-kilometer) spatial scales is computationally very expensive. This study develops a highly efficient framework for this task by coupling deep learning (DL) and physical modeling. This framework is developed and tested using regional climate simulations performed over a domain covering Montreal and adjoining regions, for the summers of 2015–2020, at 2.5 km and 250 m resolutions. The DL framework uses a recurrent approach and considers atmospheric physical processes, such as advection, to generate high-resolution information from low-resolution data, which enables it to recreate fine details and produce temporally consistent fields. The DL framework generates realistic high-resolution precipitation estimates, including intense short-duration precipitation events, which allows it to be applied in engineering problems, such as evaluating the climate resiliency of urban storm drainage systems. The results portray the value of the proposed DL framework, which can be extended to other resolutions, periods, and regions.
Progress and emerging techniques for biomaterial-based derivation of mesenchymal stem cells (MSCs) from pluripotent stem cells (PSCs)
Authors: Prakash Nityanand , Kim Jiseong , Jeon Jieun , Kim Siyeon , Arai Yoshie , Bello Alvin Bacero , Park Hansoo , Lee Soo-Hong
Published: April 2023

The use of mesenchymal stem cells (MSCs) for clinical purposes has skyrocketed in the past decade. Their multilineage differentiation potentials and immunomodulatory properties have facilitated the discovery of therapies for various illnesses. MSCs can be isolated from infant and adult tissue sources, which means they are easily available. However, this raises concerns because of the heterogeneity among the various MSC sources, which limits their effective use. Variabilities arise from donor- and tissue-specific differences, such as age, sex, and tissue source. Moreover, adult-sourced MSCs have limited proliferation potentials, which hinders their long-term therapeutic efficacy. These limitations of adult MSCs have prompted researchers to develop a new method for generating MSCs. Pluripotent stem cells (PSCs), such as embryonic stem cells and induced PSCs (iPSCs), can differentiate into various types of cells. Herein, a thorough review of the characteristics, functions, and clinical importance of MSCs is presented. The existing sources of MSCs, including adult- and infant-based sources, are compared. The most recent techniques for deriving MSCs from iPSCs, with a focus on biomaterial-assisted methods in both two- and three-dimensional culture systems, are listed and elaborated. Finally, several opportunities to develop improved methods for efficiently producing MSCs with the aim of advancing their various clinical applications are described.
Long-term cardiac effect of sacubitril-valsartan in hemodialysis patients with a reduced ejection fraction after aortic valve replacement for aortic stenosis: a case report with literature review
Authors: Daimon Shoichiro , Sakamoto Yuka , Yasuda Miyuki , Nishitani Mitsuhiro
Published: April 2023

Background

Although the angiotensin receptor-neprilysin inhibitor sacubitril-valsartan has demonstrated a valuable effect on cardiac function in patients with heart failure with a reduced ejection fraction, the effect of this agent in hemodialysis patients is not well known.

Case presentation

Sacubitril-valsartan was administered to two anuric hemodialysis patients, an 81-year-old woman and a 79-year-old man, after aortic valve replacement for aortic stenosis. Following sacubitril-valsartan administration, the two patients’ N-terminal pro-brain natriuretic peptide levels decreased from 110,373 to 47,742 and 22,723 to 7692 pg/mL within one month, respectively, and were sustained within the lower levels thereafter. Although the patients’ left ventricular ejection fractions were 40.0% and 28.4%, respectively, these values did not change at seven and four months after sacubitril-valsartan administration (41.0% and 30.0%, respectively) but increased gradually to 56.6% and 54.9% at 11 and 13 months, respectively, and were sustained at the same levels thereafter.

Conclusions

Long-term sacubitril-valsartan administration can improve cardiac function in hemodialysis patients with a reduced ejection fraction.
Circulating neutrophil extracellular trap (NET)-forming ‘rogue’ neutrophil subset, immunotype [DEspR + CD11b +], mediate multi-organ failure in COVID-19—an observational study
Authors: Herrera Victoria L. M. , Bosch Nicholas A. , Lok Judith J. , Nguyen Mai Q. , Lenae Kaitriona A. , deKay Joanne T. , Ryzhov Sergey V. , Seder David B. , Ruiz-Opazo Nelson , Walkey Allan J.
Published: April 2023

Background

Cumulative research show association of neutrophils and neutrophil extracellular traps (NETs) with poor outcomes in severe COVID-19. However, to date, there is no curative intent therapy able to block neutrophil/NETs-mediated progression of multi-organ dysfunction. Because of emerging neutrophil heterogeneity, the study of subsets of circulating NET-forming neutrophils [NET + Ns] as mediators of multi-organ failure progression among patients with COVID-19 is critical to identification of therapeutic targets.

Methods

We conducted a prospective observational study of circulating levels of CD11b + [NET + N] immunotyped for dual endothelin-1/signal peptide receptor (DEspR ±) expression by quantitative immunofluorescence-cytology and causal mediation analysis. In 36 consented adults hospitalized with mod-severe COVID-19, May to September 2020, we measured acute multi-organ failure via SOFA-scores and respiratory failure via SaO2/FiO2 (SF)-ratio at time points t1 (average 5.5 days from ICU/hospital admission) and t2 (the day before ICU-discharge or death), and ICU-free days at day28 (ICUFD). Circulating absolute neutrophil counts (ANC) and [NET + N] subset-specific counts were measured at t1. Spearman correlation and causal mediation analyses were conducted.

Results

Spearman correlation analyses showed correlations of t1-SOFA with t2-SOFA (rho rS = 0.80) and ICUFD (rS = -0.76); circulating DEspR + [NET + Ns] with t1-SOFA (rS = 0.71), t2-SOFA (rS = 0.62), and ICUFD (rS = -0.63), and ANC with t1-SOFA (rS = 0.71), and t2-SOFA (rS = 0.61).

Causal mediation analysis identified DEspR + [NET + Ns] as mediator of 44.1% [95% CI:16.5,110.6] of the causal path between t1-SOFA (exposure) and t2-SOFA (outcome), with 46.9% [15.8,124.6] eliminated when DEspR + [NET + Ns] were theoretically reduced to zero. Concordantly, DEspR + [NET + Ns] mediated 47.1% [22.0,72.3%] of the t1-SOFA to ICUFD causal path, with 51.1% [22.8,80.4%] eliminated if DEspR + [NET + Ns] were reduced to zero. In patients with t1-SOFA > 1, the indirect effect of a hypothetical treatment eliminating DEspR + [NET + Ns] projected a reduction of t2-SOFA by 0.98 [0.29,2.06] points and ICUFD by 3.0 [0.85,7.09] days. In contrast, there was no significant mediation of SF-ratio through DEspR + [NET + Ns], and no significant mediation of SOFA-score through ANC.

Conclusions

Despite equivalent correlations, DEspR + [NET + Ns], but not ANC, mediated progression of multi-organ failure in acute COVID-19, and its hypothetical reduction is projected to improve ICUFD. These translational findings warrant further studies of DEspR + [NET + Ns] as potential patient-stratifier and actionable therapeutic target for multi-organ failure in COVID-19.
Learning and teaching sustainable business in the digital era: a connectivism theory approach
Authors: Dziubaniuk Olga , Ivanova-Gongne Maria , Nyholm Monica
Published: April 2023

Higher education institutions may adopt various approaches to the pedagogic principles and methods used in teaching sustainable development in business and marketing courses. These methods can include the utilisation of digital technologies and online communication to facilitate distance learning and fast access to relevant information. Changes towards the digitalisation of the learning environment especially gained popularity during the Covid-19 pandemic. In the post-pandemic period, digitalisation continues to facilitate the learning and teaching processes. However, the implementation of digital technologies, besides technological expertise, requires appropriate theoretical frameworks for understanding how learning is developed. This study explores connectivism theory applied to the pedagogic practices of knowledge dissemination concerning sustainable development in the fields of business and marketing. Connectivism embraces knowledge as a network where the learner, with the help of digital technologies, develops mental connections between pieces of information during interaction with various information sources. This qualitative research empirically explores the principles of connectivism embedded in the learning and teaching of a university course conducted online. The research findings indicate that connectivism may be a suitable conceptual framework that motivates learners to develop knowledge through digital enablers, discussions and social networking and to make connections to sustainability concepts. The principles of connectivism may help instructors to develop a learning environment where learners add understandings to their previous knowledge on sustainability through online interactions and by accessing digital knowledge sources. This study makes several interdisciplinary contributions by deepening the insights into digital pedagogic methods and approaches for the facilitation of learning, which may be of interest to academic and other pedagogic practitioners.
Risk factors-related first episode postpartum psychosis among Egyptian women: the role of psychosocial and the biological factors
Authors: Khedr Eman M. , Ramadan Ehab S. , Osman Mohamed N. , Ahmed Gellan K.
Published: April 2023

Background

The risks associated with postpartum psychosis (PP) are poorly recognized in Egyptian women. We aimed to study the role of sociodemographic, psychosocial, obstetric, and biological factors in the occurrence of PP within 4 weeks after delivery in a sample of Egyptian women. We included 60 women with PP and 30 postpartum women without psychosis. All participants underwent a full medical assessment and psychiatric assessment using the Holmes and Rahe Stress Scale, the Brief Psychiatric Rating Scale (BPRS), and hormonal assessment (including estrogen levels and thyroid function tests) were performed for each woman.

Results

The mean age of pregnancy of women with PP was significantly younger than that of controls (19.2 ± 2.04 years versus 24.37 ± 4.92 years). PP was significantly more common among primipara (73.3%), women who underwent cesarean sections (58.3%) and had thyroid dysfunction. The rates of low birth weight, and premature delivery were significantly higher among women with PP than among those without PP. The mean time-lapse from parturition to the onset of PP symptoms was 6.11 ± 1.62 days. Sleep disturbance, and irritability symptoms were the earliest symptoms of PP in our study. Plasma estrogen levels were significantly correlated with the total BPRS scores in patients with PP (P = 0.001).

Conclusions

Young age, primiparity, low birth weight, cesarean delivery, a rapid drop in the estrogen level and thyroid dysfunction all could contribute to the occurrence of PP.
Chemopreventive potential of kimchi, an ethnic food from Korea, against colorectal carcinogenesis associated with red meat intake
Authors: Surya Reggie , Surya Ervan , Nugroho David , Romulo Andreas , Kamal Nurkhalida , Rahayu Winiati Pudji , Benchawattananon Rachadaporn , Oh Jin-Seok
Published: April 2023

Kimchi, the traditional fermented vegetables with seasonings from Korea, is globally renowned as healthy food with anticancer properties. Colorectal cancer is the world’s third leading cancer with an increasing incidence rate over the past years. High red meat intake is strongly associated with colorectal cancer, and the World Health Organization has identified red meat as probably carcinogenic to humans (Group 2A). This study aimed to investigate the chemopreventive potential of cabbage kimchi against the promotion of colorectal cancer by red meat in vivo using carcinogen-injected rats. Rats were fed by AIN-76 diet enriched in freeze-dried beef sirloin supplemented or not with kimchi powder for 120 days prior to killing. Kimchi supplementation at moderate (5%) and high (10%) concentration significantly suppressed the formation of precancerous lesions in the colon of red meat-fed rats. Using fecal water, the aqueous extract of feces, we found out that kimchi supplementation limited iron-mediated oxidation and reduced lipid peroxidation in the feces of rats. Furthermore, kimchi supplementation reduced the toxicity of fecal water of red meat-fed rats toward human colonic epithelial cells in vitro by suppressing the formation of cellular reactive oxygen species (ROS). The chemopreventive effects of kimchi were associated with the acidification of fecal matrix and increase in fecal lactic acid bacteria (LAB). Gene expression analysis in the colon of rats demonstrated that kimchi supplementation prevented colorectal carcinogenesis by up-regulating the expression of tumor-suppressor genes and antioxidant enzymes, as well as by down-regulating the expression of proinflammatory proteins. Taken together, our findings suggested that kimchi consumption is correlated with lower promotion of colorectal cancer associated with red meat intake.
Low-phospholipid associated cholelithiasis (LPAC) syndrome: an unusual form in an elderly and overweight woman
Authors: Razafindrazoto Chantelli Iamblaudiot , Ralaizanaka Behoavy Mahafaly , Rakotomalala Jolivet Auguste , Stern Christiane , Razafimahefa Soloniaina Hélio , Ramanampamonjy Rado Manitrala , Lebray Pascal
Published: April 2023

Background

Low-phospholipid associated cholelithiasis (LPAC) remains an under-diagnosed condition. It can be revealed by complications such as acute cholecystitis, acute angiocholitis and acute pancreatitis. We report a case of acute pancreatitis secondary to LPAC syndrome.

Case presentation

A 58-year-old woman was hospitalized for recurrent biliary-type abdominal pain after cholecystectomies. The diagnosis of acute biliary pancreatitis revealing a low-phospholipid associated cholelithiasis syndrome was retained after explorations. An abdominal ultrasound performed by an expert radiologist allowed us to confirm the diagnosis of LPAC syndrome, showing a comet tail image along the intrahepatic bile ducts. Ursodeoxycholic acid was started without waiting for the result of the ABCB4 mutation. The outcome was spectacular with complete disappearance of the symptoms after the first week.

Conclusion

Expert ultrasound remains the key examination for the confirmation of the diagnosis of a low-phospholipid associated cholelithiasis syndrome. It should be requested at the slightest warning signs such as a young age less than 40 years and recurrence of biliary symptoms after cholecystectomy.
Proptosis under evaluation—a rare case report on pseudolymphoma of orbit
Authors: Raguraman Sharulatha , Kushwaha Akshat , Penubarthi Lokesh Kumar
Published: April 2023

Background

Orbital pseudolymphoma is one of the rare diseases affecting the ocular adnexa and causing various symptoms requiring histopathological evidence for diagnosis and appropriate treatment with oral steroids or immunosuppressive agents. However, there is less literature available on this disease, thus adding to it will help in the early diagnosis and treatment of the patients.

Case presentation

A 48-year-old female from a village in South India came to our tertiary care centre with the only complaints of right eye protrusion for 1 year. With a working diagnosis of intraorbital mass, radiological investigations like contrast-enhanced CT and MRI were taken. It showed well-capsulated mass involving the right inferior rectus extending into the intraconal space just abutting the optic nerve. Trans-antral endoscopic biopsy under general anaesthesia was taken and reported as pseudolymphoma proven with CD 3 and CD 20 immunohistochemistry markers. The patient was treated with oral corticosteroids and tapered over a period of 3 months. During the treatment period, the patient developed no diminution of vision or new complaints.

Conclusion

Orbital pseudolymphomas are benign lymphoproliferative diseases affecting the ocular adnexal tissue. Patients can present with painless ptosis, proptosis, diplopia, or eyelid swelling. Prompt diagnosis and treatment result in the remission of the disease.
Observational viability of the intermediate DBI inflation in the presence of a minimal length
Authors: Rashidi N. , Roushan M. , Nozari K.
Published: April 2023

We consider an intermediate Dirac-Born-Infeld (DBI) inflationary model in the presence of a minimal measurable length in the theory. We show that the presence of a minimal measurable length modifies the definitions of the scalar and tensor spectral indices and also other inflation observables. This is due to modification of the momentum and corresponding wave number of the perturbations in the presence of a minimal length. By using the deformed definition of the scalar and tensor spectral indices, we perform numerical analysis on the intermediate DBI inflation model to find some constraints on the deformation parameter. In this regard, we compare our numerical results with both Planck2018 TT, TE, EE +lowE +lensing +BAO+ BK14 and Planck2018 TT, TE, EE +lowE+lensing+BK14 +BAO+LIGO and Virgo2016 data at the 68% CL and 95% CL. Our numerical study shows that the intermediate DBI inflation model in the presence of a minimal measurable length is observationally viable if the upper bound on the deformation parameter to be considered of the order of 1048 at 68% CL and 1049 at 95% CL. This is consistent with the results of other approaches to constrain such a quantity.