bluuebunny/crossref_metadata_2025 huggingface dataset:
QTL mapping reveals key factors related to the isoflavone contents and agronomic traits of soybean (Glycine max)
Authors: Kim Jung Min , Seo Ji Su , Lee Jeong Woo , Lyu Jae Il , Ryu Jaihyunk , Eom Seok Hyun , Ha Bo-Keun , Kwon Soon-Jae
Published: October 2023

Background

Soybean is a valuable source of edible protein and oil, as well as secondary metabolites that can be used in food products, cosmetics, and medicines. However, because soybean isoflavone content is a quantitative trait influenced by polygenes and environmental interactions, its genetic basis remains unclear.

Results

This study was conducted to identify causal quantitative trait loci (QTLs) associated with soybean isoflavone contents. A mutant-based F2 population (190 individuals) was created by crossing the Korean cultivar Hwanggeum with low isoflavone contents (1,558 µg g−1) and the soybean mutant DB-088 with high isoflavone contents (6,393 µg g−1). A linkage map (3,049 cM) with an average chromosome length of 152 cM was constructed using the 180K AXIOM® SoyaSNP array. Thirteen QTLs related to agronomic traits were mapped to chromosomes 2, 3, 11, 13, 19, and 20, whereas 29 QTLs associated with isoflavone contents were mapped to chromosomes 1, 3, 8, 11, 14, 15, and 17. Notably, the qMGLI11, qMGNI11, qADZI11, and qTI11, which located Gm11_9877690 to Gm11_9955924 interval on chromosome 11, contributed to the high isoflavone contents and explained 11.9% to 20.1% of the phenotypic variation. This QTL region included four candidate genes, encoding β-glucosidases 13, 14, 17–1, and 17–2. We observed significant differences in the expression levels of these genes at various seed developmental stages. Candidate genes within the causal QTLs were functionally characterized based on enriched GO terms and KEGG pathways, as well as the results of a co-expression network analysis. A correlation analysis indicated that certain agronomic traits (e.g., days to flowering, days to maturity, and plant height) are positively correlated with isoflavone content.

Conclusions

Herein, we reported that the major QTL associated with isoflavone contents was located in the interval from Gm11_9877690 to Gm11_9955924 (78 kb) on chromosome 11. Four β-glucosidase genes were identified that may be involved in high isoflavone contents of soybean DB-088. Thus, the mutant alleles from soybean DB-088 may be useful for marker-assisted selection in developing soybean lines with high isoflavone contents and superior agronomic traits.
Is the clinical frailty scale feasible to use in an emergency department setting? A mixed methods study
Authors: Hörlin Erika , Munir Ehrlington Samia , Toll John Rani , Henricson Joakim , Wilhelms Daniel
Published: October 2023

Background

The Clinical Frailty Scale (CFS) is a frailty assessment tool used to identify frailty in older patients visiting the emergency department (ED). However, the current understanding of how it is used and accepted in ED clinical practice is limited. This study aimed to assess the feasibility of CFS in an ED setting.

Methods

This was a prospective, mixed methods study conducted in three Swedish EDs where CFS had recently been introduced. We examined the completion rate of CFS assessments in relation to patient- and organisational factors. A survey on staff experience of using CFS was also conducted. All quantitative data were analysed descriptively, while free text comments underwent a qualitative content analysis.

Results

A total of 4235 visits were analysed, and CFS assessments were performed in 47%. The completion rate exceeded 50% for patients over the age of 80. Patients with low triage priority were assessed to a low degree (24%). There was a diurnal variation with the highest completion rates seen for arrivals between 6 and 12 a.m. (58%). The survey response rate was 48%. The respondents rated the perceived relevance and the ease of use of the CFS with a median of 5 (IQR 2) on a scale with 7 being the highest. High workload, forgetfulness and critical illness were ranked as the top three barriers to assessment. The qualitative analysis showed that CFS assessments benefit from a clear routine and a sense of apparent relevance to emergency care.

Conclusion

Most emergency staff perceived CFS as relevant and easy to use, yet far from all older ED patients were assessed. The most common barrier to assessment was high workload. Measures to facilitate use may include clarifying the purpose of the assessment with explicit follow-up actions, as well as formulating a clear routine for the assessment.

Registration

The study was registered on ClinicalTrials.gov 2021-06-18 (identifier: NCT04931472).
Bickerstaff’s brainstem encephalitis: a rare case of neurologic complication in Ulcerative Colitis
Authors: Joo Haram , Lee Chung Seok , Joe Sangwon , Han Jinu , Kim Han-Kyeol , Cho Hanna
Published: October 2023

Bickerstaff’s brainstem encephalitis is a rare autoimmune disorder that presents with ataxia, ophthalmoplegia, disturbance of consciousness and quadriplegia. A 45-year-old man with a history of ulcerative colitis (UC) taking mesalazine (5-aminosalicylic acid) visited the emergency room presenting with ataxia, ophthalmoplegia and a progressively worsening cognitive impairment. Cerebrospinal fluid analysis showed mild elevation in protein and white blood cell count and increased intracranial pressure. Anti-GQ1b autoantibodies were found positive in the patient’s serum and contrast-enhanced brain magnetic resonance imaging showed diffuse leptomeningeal enhancement and pontine lesions. Based on these findings and the patient’s clinical course and history, he was diagnosed with Bickerstaff’s brainstem encephalitis. Mesalazine was discontinued and high-dose steroid pulse therapy was started, followed by intravenous immunoglobulin, which resulted in gradual improvement of the neurologic symptoms. When an ulcerative colitis patient presents with progressive cognitive impairment, quadriplegia and disturbance of consciousness and gait, Bickerstaff brainstem encephalitis should be considered in the differential diagnosis and prompt immunotherapy may lead to favorable prognosis.
A comparative study of CTG monitoring one hour before labor in infants born with and without asphyxia
Authors: Nabipour Hosseini Seyedeh Tala , Abbasalizadeh Fatemeh , Abbasalizadeh Shamsi , Mousavi Sanaz , Amiri Paria
Published: October 2023

Background and Aim

Asphyxia is a condition arising when the infant is deprived of oxygen, causing Fetal brain damage or death, which is associated with hypoxia and hypercapnia. Although fetal Cardiotocography (CTG) can show the Fetal health status during labor, some studies have reported cases of fetal asphyxia despite reassuring CTGs. This study hence aimed to compare FHR Monitoring and uterine contractions in the last hour before delivered between two groups of infants born with and without asphyxia.

Methodology

The study was conducted on 70 pregnant women who delivered Taleghani and Al-Zahra academic teaching hospitals of Tabriz for labor in 2020–2021.

Results

The study data showed no significant difference between mothers of infants with and without asphyxia in terms of demographics (p > 0.05). The prevalence of asphyxia was significantly higher only in mothers with the gravidity of 3 and 4 (p = 0.003). In terms of the methods for labor induction, the use of oxytocin was more common among mothers of infants with asphyxia (74.3%) than in those of infants without asphyxia (p = 0.015). The results also revealed a significant difference between infants with and without asphyxia in the Apgar score (first, fifth, and tenth minutes), need for neonatal resuscitation, umbilical cord artery Acidosis (pH, bicarbonate, and BE), and severity of HIE between two groups of infants with asphyxia and without asphyxia (p < 0.0001). The comparison of fetal CTG 0 to 20 min before the delivery indicated that normal variability was observed in 71.4% of infants born with asphyxia, whereas this figure for infants born without asphyxia was 91.4% (p = 0.031). However, the results showed no significant difference between the two groups of infants in any of the tstudied indicators at 20 and 40 min before the labor(p > 0.05). There was a significant difference between the two groups of infants in terms of deceleration at 40 and 60 min before the labor, as it was observed in 53.6% of infants born with asphyxia and only 11.1% of those born without asphyxia. The results also demonstrated a significant difference between the two groups in the type of deceleration (p = 0.025). Pearson and Spearman correlation coefficients showed a significant and direct relationship between interpretation the CTG of the three Perinatologists(p < 0.0001, r > 0.8).

Conclusion

The study results demonstrated a significant difference between infants born with asphyxia and those born without asphyxia in variability at 0 to 20 min before the labor and deceleration at 40 to 60 min before the labor.
Navigating miscarriage in Jordan: understanding emotional responses and coping strategies
Authors: Taybeh Esra’ , Hamadneh Shereen , Al-Alami Zina , Abu-Huwaij Rana
Published: October 2023

Background

Miscarriages account for 20% of clinically confirmed pregnancies and up to 50% of all pregnancies and is considered one of the most heartbreaking events experienced by women. The current study aimed to explore participants’ perceptions and practices and how they link with the negative emotions of miscarriage.

Methods

In this cross-sectional study a web-based questionnaire was used to gather data from 355 women living in Jordan who had experienced a previous miscarriage. The questionnaire consisted of four sections, including socio-demographic information, experience with miscarriage, emotions after the experience, and self-care practices. Participants were recruited through social media platforms from April to August 2022. Data were analyzed using SPSS, and descriptive statistics, chi-square test, and binomial regression were performed to examine the results.

Results

The results show that the majority of participants were in the age group of 22–34 years and a larger percentage of participants hold a Bachelor’s degree and were employed. All participants had experienced a previous miscarriage with 53.8% having one, 27.0% having two, and 19.2% having three or more miscarriages. In addition, most miscarriages did not have an explanation for their cause (77.5%), but vaginal bleeding was the most reported symptom (55.2%) and surgical management was predominant (48.7%). Most participants reported adequate emotional support from partners and family (63.7% and 62.3%, respectively). Almost half (48.7%) of the respondents felt like they had lost a child and those who did not receive any social support had a higher association with the same feeling (p = 0.005). Of the participating women, 40.3% decided to postpone another pregnancy while 20.0% planned for a subsequent pregnancy. The feeling of shame regarding the miscarriage was the main driver for women to get pregnant again (Odd ration [OR] 2.98; 95% confidence interval (CI) 1.31–6.82; p = 0.01).

Conclusions

The findings highlight the emotional impact of miscarriage on women and the need for proper support and self-care practices.
Gender inequities in women’s access to maternal health care utilisation in Zambia: a qualitative analysis
Authors: Kalindi Audrey M. , Houle Brian , Smyth Bruce M. , Chisumpa Vesper H.
Published: October 2023

Background

The role of gender inequities in women’s ability to access maternal health care has mainly been analysed from either women’s or men’s perspective only. In this article, we explore the role of gender inequities in maternal health care utilisation from both men’s and women’s perspectives.

Methods

Thirty-six interviews were conducted with reproductive age women (n = 24), and men whose wives/partners gave birth within the last three years prior to our study in Zambia (n = 12). Our study sought to improve understanding of the normative environment in which women and men make decisions on maternal health care utilisation in Zambia.

Results

We found that men and women had different expectations regarding their gender roles in maternal health care utilisation, which created inequities reinforced by societal norms and traditions. Men make most household decisions including those related to reproductive health and they often have the major say in access to maternal health services despite not having holistic maternal health information which creates challenges in maternal health care utilisation.

Conclusion

The study highlights the need for maternal health care utilisation decisions to be made by both men and women and that men should be fully involved in maternal health care from pregnancy until after child birth. Further, there is urgent need for concerted and sustained efforts to change traditional norms that reinforce these inequities and affect maternal health care utilisation if Zambia is to meet Sustainable Development Goal-3.1.
Global prevalence of post-abortion depression: systematic review and Meta-analysis
Authors: Gebeyehu Natnael Atnafu , Tegegne Kirubel Dagnaw , Abebe Kelemu , Asefa Yibeltal , Assfaw Belete Birhan , Adella Getachew Asmare , Alemu Biresaw Wassihun , Sewyew Dagne Addisu
Published: October 2023

Background

Depression after abortion is a common problem for all women of reproductive age. However, there are not any data on post-abortion depression at a global level. Consequently, the purpose of this study was to find out the global prevalence of post-abortion depression.

Methods

The present study involved a comprehensive search of several databases, including Science Direct, Scopus, EMBSE, Google Scholar, and PubMed. The search was conducted between February 1, 2023, and March 10, 2023. The data was extracted using Microsoft Excel (version 14) and analyzed using STATA statistical software. To evaluate publication bias, a forest plot, Begg’s test, and Egger’s test were employed. Heterogeneity was assessed using I2, and a pooled estimated analysis was conducted. Additionally, subgroup analysis was performed based on the study continent/region, World Bank income group, screening instrument, and study design.

Results

This analysis included 15 papers with a total of 18,207 research participants out of a total of 657 articles. The overall pooled prevalence of post-abortion depression was found to be 34.5% (95% CI: 23.34, 45.68), with an I2value of 71.6%. The prevalence of post-abortion depression varied based on geographic location, World Health Organization (WHO) regions, World Bank income category, screening approach, and study design. The highest proportion of post-abortion depression was observed in Asia (37.5%), while the WHO’s Eastern Mediterranean region had the greatest rate of post-abortion depression (43.1%). Lower-middle-income countries had the highest frequency of post-abortion depression (42.91%) based on World Bank economic classification. The Center of Epidemiological Studies Depression Scale was found to have the highest incidence of reported depression prevalence (30%) across diagnostic tools. Furthermore, the prevalence of depression was higher in cross-sectional study designs (36.42%) compared to cohort studies (22.7%).

Conclusion

In conclusion, the occurrence of post-abortion depression has been observed to be widespread globally. The prevalence of post-abortion is found to be influenced by several factors, including the methodology employed in the study, the diagnostic tool utilized, the geographical location, and the socioeconomic status of the population. Healthcare providers should prioritize the provision of post-abortion counseling, care, and emotional support to women.
Impact of bronchoscopic thermal vapor ablation on lung volume reduction in patients with emphysema: a meta-analysis
Authors: Zhi Lijia , Liao Liping , Wu Zhi , Wang Tiezhu , Ye Yuming , Li Hao , Lin Li , Qi Jia-Chao , Zhang Liangji
Published: October 2023

Background

Bronchoscopic lung volume reduction (LVR) could significantly improve pulmonary function and quality of life in patients with emphysema. We aimed to assess the efficacy and safety of bronchoscopic thermal vapor ablation (BTVA) on LVR in patients with emphysema at different stage.

Methods

A systematic search of database including PubMed, Embase and Cochrane library was conducted to determine all the studies about bronchoscopic thermal vapor ablation published through Dec 1, 2022. Related searching terms were “lung volume reduction”, “bronchoscopic thermal vapor ablation”, “bronchial thermal vapor ablation” “BTVA” and “emphysema”, “efficacy” and”safety”. We used standardized mean difference (SMD) to analyze the summary estimates for BTVA therapy.

Results

We retrieved 30 records through database search, and 4 trials were selected for meta-analysis, including 112 patients with emphysema. Meta-analysis of the pooled effect showed that levels of forced expiratory volume in 1 s (FEV1), residual volume (RV), total lung capacity (TLC), 6-min walk distance (6MWD) and St George’s Respiratory Questionnaire (SGRQ) were significantly improved in patients with emphysema following BTVA treatment between 6 months vs. baseline. Additionally, no significant changes in FEV1, RV, TLC and SGRQ occurred from 3 to 6 months of follow-up except for 6MWD. The magnitude of benefit was higher at 3 months compared to 6 months. The most common complications at 6 months were treatment-related chronic obstructive pulmonary disease (COPD) exacerbations (RR: 12.49; 95% CI: 3.06 to 50.99; p < 0.001) and pneumonia (RR: 9.49; 95% CI: 2.27 to 39.69; p < 0.001).

Conclusions

Our meta-analysis provided clinically relevant information about the impact and safety of BTVA on predominantly upper lobe emphysema. Particularly, short-term significant improvement of lung function and quality of life occurred especially within the initial 3 months. Further large-scale, well-designed long-term interventional investigations are needed to clarify this issue.
Oscillometry of the respiratory system in Parkinson's disease: physiological changes and diagnostic use
Authors: Caldas Bruno Tavares , Ribeiro Fernando Carlos Vetromille , Pereira João Santos , Souza Wilma Costa , Lopes Agnaldo José , de Melo Pedro Lopes
Published: October 2023

Background

Lung function analysis in Parkinson's disease (PD) is often difficult due to the demand for adequate forced expiratory maneuvers. Respiratory oscillometry exams require onlyquiet tidal breathing and provide a detailed analysis of respiratory mechanics. We hypothesized that oscillometry would simplify the diagnosis of respiratory abnormalitiesin PD and improve our knowledge about the pathophysiological changes in these patients.

Materials and methods

This observational study includes 20 controls and 47 individuals with PD divided into three groups (Hoehn and Yahr Scale 1–1.5; H&Y scale 2–3 and PD smokers).The diagnostic accuracy was evaluated by investigating the area under the receiver operating characteristic curve (AUC).

Results

Initial stages are related to increased peripheral resistance (Rp; p = 0.001). In more advanced stages, a restrictive pattern is added, reflected by reductions in dynamic compliance (p < 0.05) and increase in resonance frequency (Fr; p < 0.001). Smoking PD patients presented increased Rp (p < 0.001) and Fr (p < 0.01). PD does not introduce changes in the central airways. Oscillometric changes were correlated with respiratory muscle weakness (R = 0.37, p = 0.02). Rp showed adequate accuracy in the detection of early respiratory abnormalities (AUC = 0.858), while in more advanced stages, Fr showed high diagnostic accuracy (AUC = 0.948). The best parameter to identify changes in smoking patients was Rp (AUC = 0.896).

Conclusion

The initial stages of PD are related to a reduction in ventilation homogeneity associated with changes in peripheral airways. More advanced stages also include a restrictive ventilatory pattern. These changes were correlated with respiratory muscle weakness and were observed in mild and moderate stages of PD in smokers and non-smokers. Oscillometry may adequately identify respiratory changes in the early stages of PD and obtain high diagnostic accuracy in more advanced stages of the disease.
Factors associated with nurses’ attitudes for providing oral care in geriatric care facilities: a cross-sectional study
Authors: Chen Mengxia , Weng Yanqiu , Zhang Jingwen , Gu Liyan , Chen Wenyao , Qiao Mengting , Wang Mengdi , Huang Xiaorong , Chen Lan , Zhang Lingjuan
Published: October 2023

Background

The world’s population is getting older. This issue is accompanied by a rise in the number of older people suffering from dementia and disability, for whom oral hygiene care is challenging. Nurses’ attitudes toward providing oral care (POC) are critical for the elderly, while few studies have investigated the determinant factors of nurses’ attitudes by identifying the current work pressure, resilience and self-efficacy in geriatric care facilities (GCFs). It is of great significance to explore the nurses’ attitudes toward POC and associated influencing factors related to psychological aspects including resilience, self-efficacy, and stress from the workplace.

Methods

Attitudes for Providing Mouth Care (A-PMC) in Chinese version were used in this cross-sectional study with 160 nurses in 2 GCFs. Data were collected using online questionnaires and analyzed by multiple linear regression analysis. Statistically significant values were considered at p < 0.05.

Results

A total of 160 nurses participated in this study, with an average age of 32.86 ± 7.43. The mean score for the A-PMC was 2.81 ± 0.47. The score of A-PMC was negatively correlated with work pressure (r=-0.332, p < 0.01), and positively correlated with resilience (r = 0.735, p < 0.01) and self-efficacy (r = 0.425, p < 0.01) respectively. Multiple linear regression analyses identified that the potential influencing factors of A-PMC were education background, work hours every shift, self-efficacy, work pressure and resilience.

Conclusions

The study results indicate nurses’ attitudes regarding PMC were at a low level, which is influenced by many factors. To improve nurses’ attitudes toward PMC and the oral hygiene (OH) of the elderly in GCFs, it is necessary to increase nurses’ education and training, establish a reasonable and effective incentive mechanism to improve nurses’ work motivation and other intervention measures to reduce work pressure.
Continuous deep sedation at the end of life: a qualitative interview-study among health care providers on an evolving practice
Authors: Heijltjes Madelon T , van Thiel Ghislaine JMW , Rietjens Judith AC , van der Heide Agnes , Hendriksen Geeske , van Delden Johannes JM
Published: October 2023

Background

Continuous deep sedation (CDS) can be used for patients at the end of life who suffer intolerably from severe symptoms that cannot be relieved otherwise. In the Netherlands, the use of CDS is guided by an national guideline since 2005. The percentage of patients for whom CDS is used increased from 8% of all patients who died in 2005 to 18% in 2015. The aim of this study is to explore potential causes of the rise in the use of CDS in the Netherlands according to health care providers who have been participating in this practice.

Methods

Semi-structured interviews were conducted and thematically analysed. Participants were Dutch health care providers (HCPs), working at patients’ homes, hospices, elderly care facilities and in hospitals and experienced in providing CDS, who were recruited via purposeful sampling.

Results

41 Health care providers participated in an interview. For these HCPs the reason to start CDS is often a combination of symptoms resulting in a refractory state. HCPs indicated that symptoms of non-physical origin are increasingly important in the decision to start CDS. Most HCPs felt that suffering at the end of life is less tolerated by patients, their relatives, and sometimes by HCPs; they report more requests to relieve suffering by using CDS. Some HCPs in our study have experienced increasing pressure to perform CDS. Some HCPs stated that they more often used intermittent sedation, sometimes resulting in CDS.

Conclusions

This study provides insight into how participating HCPs perceive that their practice of CDS changed over time. The combination of a broader interpretation of refractory suffering by HCPs and a decreased tolerance of suffering at the end of life by patients, their relatives and HCPs, may have led to a lower threshold to start CDS.

Trial registration

The Research Ethics Committee of University Medical Center Utrecht assessed that the study was exempt from ethical review according to Dutch law (Protocol number 19–435/C).
The effect of Moringa oleifera crude extract on liver cell line, HepG2
Authors: Sowunmi Boluwatife O. , Gonzo Martin
Published: October 2023

Background

The liver plays a crucial role in the body's metabolic and detoxification processes. Given its importance, compromised liver function can negatively impact the body’s metabolic and physiological function. Liver diseases can result from several factors, including exposure to toxins, alcohol consumption, and viral infections. Therefore, finding natural remedies for liver protection and treatment is important. Moringa oleifera is a tree known for its various medicinal properties, including hepatoprotective effects. This study aimed to investigate the potential of M. oleifera seed extract in protecting liver cells.

Methods

In this study, dried-seed powder of M. oleifera was extracted using extraction solvents, methanol, and ethanol. HepG2 cells were cultured and treated with different concentrations of the extracts. The antioxidative activity, cell viability, and antiproliferation were assessed using the total antioxidant capacity assay (TAC) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Additionally, liver enzyme activity was determined through alkaline phosphatase and aspartate aminotransferase activity assays.

Results

The extracts had varying effects on liver cells depending on the concentration and time of exposure. Lower concentrations (50 mg/l and 100 mg/l) have mild stimulatory effects/minimal impact on metabolic activity, while higher concentrations (200 mg/l and 400 mg/l) tend to decrease metabolic activity, especially at later time points. Moreover, the extracts effectively reduced the levels of the liver enzyme AST, indicating their ability to mitigate liver injury.

Conclusion

The study concludes that the crude extracts of M. oleifera seeds exhibit potential as a natural remedy for liver diseases. The effects of M. oleifera extract suggest that it has potential as a preventive and therapeutic agent for liver damage. This study highlights the importance of exploring natural remedies for liver protection and treatment.
Opportunities and challenges in clinical learning of midwifery students in public Universities of Tigray Region, Ethiopia, 2020: a qualitative study
Authors: Abraha Tomas Amare , W/tensay Kidisti Tesfay , Gebre Merhawi Birhane , Abrha Birhanu Abadi , Haile Gebrhud Berihu
Published: October 2023

Background

Clinical learning focuses on real problems in the context of professional practice in which learners are motivated by its relevance and active participation. Studies showed that midwifery students were challenged by the absence of a variety of cases in non-teaching hospitals, overcrowded teaching hospitals, absence of objective-based evaluation methods, and lack of supervision from clinical instructors. If the theory learned in class was applied in practice, it is helpful to produce skillful and competent midwifery professionals. The aim of this study was exploring opportunities and challenges for midwifery students in the clinical learning environment.

Methods

the study was conducted in public Universities of Tigray, Ethiopia. Phenomenology study design and purposive sampling technique were employed; four focused group discussions and five key informant interviews were conducted. Data were collected using an open-ended guide, transcribed verbatim, entered into ATLAS ti7 software, and translated. Then codes and themes were derived from the transcribed data, and finally analyzed thematically.

Results

a total of 33 participants in which 28 in four focused group discussions and five key informant interviews participated in this study. Based on the result, midwifery students were getting opportunities to practice when they were assigned to non-teaching hospitals, working with close supervision, having smooth relationships with staff, receiving constructive feedback, and evaluated based on their skills. Whereas, they were challenged by aggressive staff, poor follow up, overcrowded teaching hospitals, low usage of skills lab, and short time for clinical practice.

Conclusion

Midwifery students have positive attitude, and were getting opportunities to practice while they were assigned to a very conducive clinical learning environment with supportive and skillful clinical instructors/ preceptors. However, they have negative attitude, and were challenged to work due to the poor attention given to midwifery students’ clinical learning. It is recommended that midwifery students have to practice well in skills lab before they assigned for clinical practice so that the skills lab have to be strengthen with all necessary materials for clinical practice and clinical instructors have to be integrated to teaching hospitals so as to educate students while their hands-on.
Agarose spot migration assay to measure the chemoattractant potential of extracellular vesicles: applications in regenerative medicine and cancer metastasis
Authors: Clos-Sansalvador Marta , Monguió-Tortajada Marta , Grau-Leal Ferran , Ruiz de Porras Vicenç , Garcia Sergio G. , Sanroque-Muñoz Marta , Font-Morón Miriam , Franquesa Marcella , Borràs Francesc E.
Published: October 2023

Background

The recruitment of effector cells is one of the novel functions described for extracellular vesicles (EVs) that needs further study. For instance, cell recruitment by mesenchymal stromal cell derived-EVs (MSC-EVs) is one of the features by which MSC-EVs may induce regeneration and ameliorate tissue injury. On the other hand, increasing evidence suggests that cancer EVs play an important role in the preparation of the pre-metastatic niche (PMN) by recruiting their primary tumour cells. Understanding and measuring the potential of MSC-EVs or cancer-EVs to induce cell migration and recruitment is essential for cell-free therapeutic approaches and/or for a better knowledge of cancer metastasis, respectively. In this context, classical in vitro migration assays do not completely mimic the potential situation by which EVs exert their chemotactic capacity.

Results

We adapted an agarose spot migration assay as an in vitro system to evaluate the cell recruitment capacity of locally delivered or localized EVs. Cell migration was tracked for 12 h or 48 h, respectively. Thereafter, endpoint migration images and time-lapse videos were analysed to quantify several parameters aiming to determine the migration of cells to either MSC-EV or pro-metastatic EV. The number of cells contained inside the agarose spots, the migration distance, the area occupied by cells, the directionality of the cell movement, and the Euclidean distance were measured. This multi-parametric evaluation revealed the potential of different MSC-EV preparations to recruit endothelial cells and to detect an enhanced recruitment capacity of highly metastatic PC3-derived EVs (PC3-EVs) compared to low-metastatic LNCaP-EVs in a tumour cell-specific manner.

Conclusions

Overall, this agarose spot migration assay may offer a diversity of measurements and migration settings not provided by classical migration assays and reveal its potential use in the EV field in two different contexts with recruitment in common: regeneration and cancer metastasis.
Arrhythmogenic left ventricular cardiomyopathy caused by a novel likely pathogenic DSP mutation, p.K1165Rfs*8, in a family with sudden cardiac death
Authors: Azimi Amir , Pourirahim Maryam , Houshmand Golnaz , Adimi Sara , Maleki Majid , Kalayinia Samira
Published: October 2023

Objective

We conducted an investigation into the clinical and molecular characteristics of Arrhythmogenic left ventricular cardiomyopathy (ALVC) caused by a novel likely pathogenic mutation in an Iranian pedigree with sudden cardiac death (SCD).

Background

ALVC is a genetically inherited myocardial disease characterized by the substitution of fibro-fatty tissue in the left ventricular myocardium, predominantly inherited in an autosomal dominant pattern and is commonly associated with genes involved in encoding desmosomal proteins, specifically Desmoplakin (DSP).

Methods

The patient and available family members underwent a comprehensive clinical assessment, including Cardiac magnetic resonance (CMR) imaging, along with Whole-exome sequencing (WES). The identified variant was confirmed and segregated by Polymerase chain reaction (PCR) and Sanger sequencing in the family members.

Results

A novel likely pathogenic heterozygous variant, DSP (NM_004415.4), c.3492_3498del, p.K1165Rfs*8 was discovered in the proband. This variant is likely to be the primary reason for ALVC in this specific family. This variant was confirmed by Sanger sequencing and segregated in other affected members of the family.

Conclusion

We identified a novel likely pathogenic variant in the DSP gene, which has been identified as the cause of ALVC in an Iranian family. Our investigation underscores the importance of genetic testing, specifically WES, for individuals suspected of ALVC and have a family history of SCD.
Urinary fluoride levels and metal co-exposures among pregnant women in Los Angeles, California
Authors: Malin Ashley J. , Hu Howard , Martínez-Mier E. Angeles , Eckel Sandrah P. , Farzan Shohreh F. , Howe Caitlin G. , Funk William , Meeker John D. , Habre Rima , Bastain Theresa M. , Breton Carrie V.
Published: October 2023

Background

Fluoride is ubiquitous in the United States (US); however, data on biomarkers and patterns of fluoride exposure among US pregnant women are scarce. We examined specific gravity adjusted maternal urinary fluoride (MUFsg) in relation to sociodemographic variables and metal co-exposures among pregnant women in Los Angeles, California.

Methods

Participants were from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) cohort. There were 293 and 490 women with MUFsg measured during first and third trimesters, respectively. An intra-class correlation coefficient examined consistency of MUFsg between trimesters. Kruskal–Wallis and Mann-Whitney U tests examined associations of MUFsg with sociodemographic variables. Covariate adjusted linear regression examined associations of MUFsg with blood metals and specific gravity adjusted urine metals among a subsample of participants within and between trimesters. A False Discovery Rate (FDR) correction accounted for multiple comparisons.

Results

Median (IQR) MUFsg was 0.65 (0.5) mg/L and 0.8 (0.59) mg/L, during trimesters one and three respectively. During both trimesters, MUFsg was higher among older participants, those with higher income, and White, non-Hispanic participants than Hispanic participants. MUFsg was also higher for White, non-Hispanic participants than for Black, non-Hispanic participants in trimester three, and for those with graduate training in trimester one. MUFsg was negatively associated with blood mercury in trimester one and positively associated with blood lead in trimester three. MUFsg was positively associated with various urinary metals, including antimony, barium, cadmium, cobalt, copper, lead, nickel, tin, and zinc in trimesters one and/or three.

Conclusions

MUFsg levels observed were comparable to those found in pregnant women in Mexico and Canada that have been associated with poorer neurodevelopmental outcomes. Lower urinary fluoride levels among Hispanic and non-Hispanic Black participants in MADRES compared to non-Hispanic White participants may reflect lower tap water consumption or lower fluoride exposure from other sources. Additional research is needed to examine whether MUFsg levels observed among pregnant women in the US are associated with neurodevelopmental outcomes.
circPSD3 is a promising inhibitor of uPA system to inhibit vascular invasion and metastasis in hepatocellular carcinoma
Authors: Xu Liangliang , Wang Peng , Li Li , Li Lian , Huang Yang , Zhang Yanfang , Zheng Xiaobo , Yi Pengsheng , Zhang Ming , Xu Mingqing
Published: October 2023

Background

Vascular invasion is a major route for intrahepatic and distant metastasis in hepatocellular carcinoma (HCC) and is a strong negative prognostic factor. Circular RNAs (circRNAs) play important roles in tumorigenesis and metastasis. However, the regulatory functions and underlying mechanisms of circRNAs in the development of vascular invasion in HCC are largely unknown.

Methods

High throughput sequencing was used to screen dysregulated circRNAs in portal vein tumor thrombosis (PVTT) tissues. The biological functions of candidate circRNAs in the migration, vascular invasion, and metastasis of HCC cells were examined in vitro and in vivo. To explore the underlying mechanisms, RNA sequencing, MS2-tagged RNA affinity purification, mass spectrometry, and RNA immunoprecipitation assays were performed.

Results

circRNA sequencing followed by quantitative real-time PCR (qRT-PCR) revealed that circRNA pleckstrin and Sect. 7 domain containing 3 (circPSD3) was significantly downregulated in PVTT tissues. Decreased circPSD3 expression in HCC tissues was associated with unfavourable characteristics and predicted poor prognosis in HCC. TAR DNA-binding protein 43 (TDP43) inhibited the biogenesis of circPSD3 by interacting with the downstream intron of pre-PSD3. circPSD3 inhibited the intrahepatic vascular invasion and metastasis of HCC cells in vitro and in vivo. Serpin family B member 2 (SERPINB2), an endogenous bona fide inhibitor of the urokinase-type plasminogen activator (uPA) system, is the downstream target of circPSD3. Mechanistically, circPSD3 interacts with histone deacetylase 1 (HDAC1) to sequester it in the cytoplasm, attenuating the inhibitory effect of HDAC1 on the transcription of SERPINB2. In vitro and in vivo studies demonstrated that circPSD3 is a promising inhibitor of the uPA system.

Conclusions

circPSD3 is an essential regulator of vascular invasion and metastasis in HCC and may serve as a prognostic biomarker and therapeutic target.
Ceramide synthase 4 overexpression exerts oncogenic properties in breast cancer
Authors: Kim Su-Jeong , Seo Incheol , Kim Min Hee , Park Joo-Won , Kim Shin , Park Woo-Jae
Published: October 2023

Background

Ceramide, a bioactive signaling sphingolipid, has long been implicated in cancer. Members of the ceramide synthase (CerS) family determine the acyl chain lengths of ceramides, with ceramide synthase 4 (CerS4) primarily generating C18–C20-ceramide. Although CerS4 is known to be overexpressed in breast cancer, its role in breast cancer pathogenesis is not well established.

Methods

To investigate the role of CerS4 in breast cancer, public datasets, including The Cancer Genome Atlas (TCGA) and two Gene Expression Omnibus (GEO) datasets (GSE115577 and GSE96058) were analyzed. Furthermore, MCF-7 cells stably overexpressing CerS4 (MCF-7/CerS4) as a model for luminal subtype A (LumA) breast cancer were produced, and doxorubicin (also known as Adriamycin [AD])-resistant MCF-7/ADR cells were generated after prolonged treatment of MCF-7 cells with doxorubicin. Kaplan–Meier survival analysis assessed the clinical significance of CERS4 expression, while Student’s t-tests or Analysis of Variance (ANOVA) compared gene expression and cell viability in different MCF-7 cell lines.

Results

Analysis of the public datasets revealed elevated CERS4 expression in breast cancer, especially in the most common breast cancer subtype, LumA. Persistent CerS4 overexpression in MCF-7 cells activated multiple cancer-associated pathways, including pathways involving sterol regulatory element–binding protein, nuclear factor kappa B (NF-κB), Akt/mammalian target of rapamycin (mTOR), and β-catenin. Furthermore, MCF-7/CerS4 cells acquired doxorubicin, paclitaxel, and tamoxifen resistance, with concomitant upregulation of ATP-binding cassette (ABC) transporter genes, such as ABCB1, ABCC1, ABCC2, ABCC4, and ABCG2. MCF-7/CerS4 cells were characterized by increased cell migration and epithelial–mesenchymal transition (EMT). Finally, CERS4 knockdown in doxorubicin-resistant MCF-7/ADR cells resulted in reduced activation of cancer-associated pathways (NF-κB, Akt/mTOR, β-catenin, and EMT) and diminished chemoresistance, accompanied by ABCB1 and ABCC1 downregulation.

Conclusions

Chronic CerS4 overexpression may exert oncogenic effects in breast cancer via alterations in signaling, EMT, and chemoresistance. Therefore, CerS4 may represent an attractive target for anticancer therapy, especially in LumA breast cancer.
Current knowledge and potential intervention of hexosamine biosynthesis pathway in lung cancer
Authors: Zou Yi , Liu Zongkai , Liu Wenjia , Liu Zhaidong
Published: October 2023

Lung cancer is a highly prevalent malignancy characterized by significant metabolic alterations. Understanding the metabolic rewiring in lung cancer is crucial for the development of effective therapeutic strategies. The hexosamine biosynthesis pathway (HBP) is a metabolic pathway that plays a vital role in cellular metabolism and has been implicated in various cancers, including lung cancer. Abnormal activation of HBP is involved in the proliferation, progression, metastasis, and drug resistance of tumor cells. In this review, we will discuss the function and regulation of metabolic enzymes related to HBP in lung cancer. Furthermore, the implications of targeting the HBP for lung cancer treatment are also discussed, along with the challenges and future directions in this field. This review provides a comprehensive understanding of the role and intervention of HBP in lung cancer. Future research focusing on the HBP in lung cancer is essential to uncover novel treatment strategies and improve patient outcomes.
Surgical management of craniospinal axis malignant peripheral nerve sheath tumors: a single-institution experience and literature review
Authors: Chowdhury Ajmain , Vivanco-Suarez Juan , Teferi Nahom , Belzer Alex , Al-Kaylani Hend , Challa Meron , Lee Sarah , Buatti John M. , Hitchon Patrick
Published: October 2023

Background

Malignant peripheral nerve sheath tumor (MPNST) is an exceedingly rare and aggressive tumor, with limited literature on its management. Herein, we present our series of surgically managed craniospinal MPNSTs, analyze their outcomes, and review the literature.

Methods

We retrospectively reviewed surgically managed primary craniospinal MPNSTs treated at our institution between January 2005 and May 2023. Patient demographics, tumor features, and treatment outcomes were assessed. Neurological function was quantified using the Frankel grade and Karnofsky performance scores. Descriptive statistics, rank-sum tests, and Kaplan–Meier survival analyses were performed.

Results

Eight patients satisfied the inclusion criteria (4 male, 4 female). The median age at presentation was 38 years (range 15–67). Most tumors were localized to the spine (75%), and 3 patients had neurofibromatosis type 1. The most common presenting symptoms were paresthesia (50%) and visual changes (13%). The median tumor size was 3 cm, and most tumors were oval-shaped (50%) with well-defined borders (75%). Six tumors were high grade (75%), and gross total resection was achieved in 5 patients, with subtotal resection in the remaining 3 patients. Postoperative radiotherapy and chemotherapy were performed in 6 (75%) and 4 (50%) cases, respectively. Local recurrence occurred in 5 (63%) cases, and distant metastases occurred in 2 (25%). The median overall survival was 26.7 months. Five (63%) patients died due to recurrence.

Conclusions

Primary craniospinal MPNSTs are rare and have an aggressive clinical course. Early diagnosis and treatment are essential for managing these tumors. In this single-center study with a small cohort, maximal resection, low-grade pathology, young age (< 30), and adjuvant radiotherapy were associated with improved survival.
Breast cancer organoids and their applications for precision cancer immunotherapy
Authors: Guan Dandan , Liu Xiaozhen , Shi Qingyang , He Bangjie , Zheng Chaopeng , Meng Xuli
Published: October 2023

Immunotherapy is garnering increasing attention as a therapeutic strategy for breast cancer (BC); however, the application of precise immunotherapy in BC has not been fully studied. Further studies on BC immunotherapy have a growing demand for preclinical models that reliably recapitulate the composition and function of the tumor microenvironment (TME) of BC. However, the classic two-dimensional in vitro and animal in vivo models inadequately recapitulate the intricate TME of the original tumor. Organoid models which allow the regular culture of primitive human tumor tissue are increasingly reported that they can incorporate immune components. Therefore, organoid platforms can be used to replicate the BC–TME to achieve the immunotherapeutic reaction modeling and facilitate relevant preclinical trial. In this study, we have investigated different organoid culture methods for BC–TME modeling and their applications for precision immunotherapy in BC.
Longitudinal changes of oxidative stress and PON1 lactonase activity and status in older pregnant women undergoing assisted reproductive technology: a prospective nested case-control study
Authors: Jiang Chenyu , Chen Meng , Wu Yujie , Bai Huai , Liu Xinghui , Fan Ping
Published: October 2023

Background

Childbearing in women with advanced maternal age (AMA) has increased the need for artificial reproductive technology (ART). ART and oxidative stress are associated with many pregnancy complications. Paraoxonase (PON) 1 is one of the key components responsible for antioxidative activity in high-density lipoprotein (HDL). This study aimed to investigate the longitudinal changes of oxidative stress and PON1 lactonase activity and status in older women undergoing ART.

Methods

This prospective nested case-control study included 129 control and 64 ART women. Blood samples were obtained respectively at different stages of pregnancy. PON1 level and lactonase activity were assessed using 7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin (DEPCyMC) and 5-thiobutyl butyrolactone (TBBL) as a substrate, respectively. A normalized lactonase activity (NLA) was estimated based on the ratio of TBBLase to DEPCyMCase activity. Serum total oxidant status (TOS), total antioxidant capacity (TAC), malondialdehyde (MDA), homocysteine (HCY), PON1 C-108T and Q192R genetic polymorphisms, and metabolic parameters were analyzed.

Results

Lactonase activity and level of PON1 gradually decreased with pregnancy progression, while glycolipid metabolism parameters and TAC levels increased with pregnancy progression or significantly raised during the 2nd and 3rd trimesters, and NLA of PON1, TOS, OSI, MDA, and HCY significantly increased before delivery in the ART and control groups. Compared with the control women, the ART women had substantially higher or relatively high lactonase activity and NLA of PON1 and TAC during pregnancy; higher triglyceride (TG), total cholesterol, low-density lipoprotein cholesterol, atherogenic index, apolipoprotein (apo) B, and apoB/apoA1 ratio in the 1st trimester; and higher fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance, and TG levels before delivery. No significant differences were found in the frequencies of PON1 C-108T and Q192R genotypes and alleles between the ART and control groups.

Conclusions

Women with AMA undergoing ART had higher TAC, PON1 lactonase activity, and PON1 NLA than control women, suggesting increased compensatory antioxidant capacity in ART women, thus showing higher sensitivity to oxidative stress-related injury and diseases.