bluuebunny/crossref_metadata_2025 huggingface dataset:
Post-bariatric pregnancy is associated with vitamin K1 deficiency, a case control study
Authors: Bechensteen Brit Torunn , Sithiravel Cindhya , Strøm-Roum Ellen Marie , Ruud Heidi Kathrine , Kravdal Gunnhild , Winther Jacob A. , Valderhaug Tone G.
Published: April 2024

Background

Maternal obesity is associated with adverse outcome for pregnancy and childbirths. While bariatric surgery may improve fertility and reduce the risk of certain pregnancy-related complications such as hypertension and gestational diabetes mellitus, there is a lack of evidence on the optimal nutritional monitoring and supplementation strategies in pregnancy following bariatric surgery. We aimed to assess the impact of bariatric surgery on micronutrients in post-bariatric pregnancy and possible differences between gastric bypass surgery and sleeve gastrectomy.

Methods

In this prospective case control study, we recruited 204 pregnant women (bariatric surgery n = 59 [gastric bypass surgery n = 26, sleeve gastrectomy n = 31, missing n = 2] and controls n = 145) from Akershus university hospital in Norway. Women with previous bariatric surgery were consecutively invited to study participation at referral to the clinic for morbid obesity and the controls were recruited from the routine ultrasound screening in gestational week 17–20. A clinical questionnaire was completed and blood samples were drawn at mean gestational week 20.4 (SD 4.5).

Results

The women with bariatric surgery had a higher pre-pregnant BMI than controls (30.8 [SD 6.0] vs. 25.2 [5.4] kg/m2, p < 0.001). There were no differences between groups regarding maternal weight gain (bariatric surgery 13.3 kg (9.6) vs. control 14.8 kg (6.5), p = 0.228) or development of gestational diabetes (n = 3 [5%] vs. n = 7 [5%], p = 1.000). Mean levels of vitamin K1 was lower after bariatric surgery compared with controls (0.29 [0.35] vs. 0.61 [0.65] ng/mL, p < 0.001). Multiadjusted regression analyses revealed an inverse relationship between bariatric surgery and vitamin K1 (B -0.26 ng/mL [95% CI -0.51, -0.04], p = 0.047) with a fivefold increased risk of vitamin K1 deficiency in post-bariatric pregnancies compared with controls (OR 5.69 [1.05, 30.77] p = 0.044). Compared with sleeve gastrectomy, having a previous gastric bypass surgery was associated with higher risk of vitamin K1 deficiency (OR 17.1 [1.31, 223.3], p = 0.030).

Conclusion

Post-bariatric pregnancy is negatively associated with vitamin K1 with a higher risk of vitamin K1 deficiency in pregnancies after gastric bypass surgery compared with after sleeve gastrectomy. Vitamin K1 deficiency in post-bariatric pregnancy have potential risk of hypocoaguble state in mother and child and should be explored in future studies.
Impact of thyroid autoimmunity on the cumulative live birth rates after IVF/ICSI treatment cycles
Authors: Huang Ning , Chen Lixue , Yan Zhiqiang , Chi Hongbin , Qiao Jie
Published: April 2024

Background

Cumulative live birth rate (CLBR) is considered as the most important endpoint for assessing the probability of having a baby in a complete in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment cycle. Many previous studies have focused on the association between thyroid autoimmunity (TAI) and live birth rate after first embryo transfer cycle, however, evidence on whether the presence of TAI affects the CLBR is lacking. The purpose of this study is to investigate the impact of TAI on the CLBR in a complete IVF/ICSI cycle.

Methods

This retrospective study included 12,796 women who underwent their first IVF/ICSI treatment between January 2019 and February 2021. Based on the levels of thyroid antibodies, 2,603 women were assigned to the TAI group, and 10,193 women were assigned to the control group. Subgroup analysis was performed according to the different causes of infertility (including male factor only, ovulation disorder, tubal factor, endometriosis and unexplained infertility) and different types and titres of thyroid antibodies. The primary outcome in this study was CLBR, which included live births from the fresh embryo transfer cycle and all subsequent frozen-thawed embryo transfer cycles performed before December 2021.

Results

There was no significant difference in the CLBR between the TAI and control groups, even after adjusting for relevant confounders including age, body mass index, cause of infertility, thyroid function, protocols of controlled ovarian stimulation, type of transfer (fresh vs. frozen), type of transferred embryo (cleavage-stage embryo vs. blastocyst), and fertilization method (IVF vs. ICSI) (cumulative live birth: 50.6% vs. 52.1%, OR 0.94, 95% CI 0.86–1.02, adjusted OR 0.97, 95%CI 0.89–1.06). Subgroup analysis showed that no significant difference was observed in CLBR between the TAI and control groups for all causes of infertility, except for infertility attributed to endometriosis. Among women with endometriosis, the CLBR was significantly lower in the TAI group than that in the control group; however, this difference was not significant after adjusting for potential confounders including age, body mass index, thyroid function, protocols of controlled ovarian stimulation, type of transfer (fresh vs. frozen), type of transferred embryo (cleavage-stage embryo vs. blastocyst), and fertilization method (IVF vs. ICSI) (cumulative live births: 43.1% vs. 51.0%, OR 0.73, 95% CI 0.53–0.99, adjusted OR 0.74, 95% CI 0.53–1.02). Another subgroup analysis demonstrated that the type and titre of thyroid antibody did not affect CLBR in women with TAI.

Conclusions

In our study, there was no significant difference in the CLBR between women with TAI and those without TAI, which suggests that TAI did not affect the chances of having a baby in a complete IVF/ICSI treatment cycle.
Concordance between SARS-CoV-2 index individuals and their household contacts on index individual COVID-19 transmission cofactors: a comparison of self-reported and contact-reported information
Authors: Dahl Angela M. , Brown Clare E. , Brown Elizabeth R. , O’Brien Meagan P. , Barnabas Ruanne V.
Published: April 2024

Background

Following the outbreak of the COVID-19 pandemic, several clinical trials have evaluated postexposure prophylaxis (PEP) among close contacts of an index individual with a confirmed SARS-CoV-2 infection. Because index individuals do not directly inform the efficacy of prevention interventions, they are seldom enrolled in COVID-19 PEP studies. However, adjusting for prognostic covariates such as an index individual’s COVID-19 illness and risk behaviors can increase precision in PEP efficacy estimates, so approaches to accurately collecting this information about the index individual are needed. This analysis aimed to assess whether surveying household contacts captures the same information as surveying the index individual directly.

Methods

REGN 2069/CoVPN 3502, a randomized controlled trial of COVID-19 PEP, enrolled household contacts of SARS-CoV-2 index individuals. CoVPN 3502-01 retrospectively enrolled and surveyed the index individuals. We compared responses to seven similar questions about the index individuals’ transmission cofactors that were asked in both studies. We estimated the percent concordance between index individuals and their household contacts on each question, with 50% concordance considered equivalent to random chance.

Results

Concordance between index individuals and contacts was high on the most objective questions, approximately 97% (95% CI: 90–99%) for index individual age group and 96% (88–98%) for hospitalization. Concordance was moderate for symptoms, approximately 85% (75–91%). Concordance on questions related to the index individual’s behavior was only slightly better or no better than random: approximately 62% (51–72%) for whether they received COVID-19 treatment, 68% (57–77%) for sharing a bedroom, 70% (59–79%) for sharing a common room, and 49% (39–60%) for mask wearing at home. However, while contacts were surveyed within 96 h of the index individual testing positive for SARS-CoV-2, the median time to enrollment in CoVPN 3502-01 was 240 days, which may have caused recall bias in our results.

Conclusions

Our results suggest a need to survey index individuals directly in order to accurately capture their transmission cofactors, rather than relying on their household contacts to report on their behavior. The lag in enrolling participants into CoVPN 3502-01 also highlights the importance of timely enrollment to minimize recall bias.
Associations between sleep duration, sleep disturbance and cardiovascular disease biomarkers among adults in the United States
Authors: Addo Prince Nii Ossah , Mundagowa Paddington T. , Zhao Longgang , Kanyangarara Mufaro , Brown Monique J. , Liu Jihong
Published: April 2024

Background

Sleep problems are associated with abnormal cardiovascular biomarkers and an increased risk of cardiovascular diseases (CVDs). However, studies investigating associations between sleep problems and CVD biomarkers have reported conflicting findings. This study examined the associations between sleep problems and CVD biomarkers in the United States.

Methods

Data were from the National Health and Nutrition Examination Survey (NHANES) (2007–2018) and analyses were restricted to adults ≥ 20 years (n = 23,749). CVD biomarkers [C-reactive Protein (CRP), low-density lipoproteins, high-density lipoproteins (HDL), triglycerides, insulin, glycosylated hemoglobin (HbA1c), and fasting blood glucose] were categorized as abnormal or normal using standardized cut-off points. Sleep problems were assessed by sleep duration (short [≤ 6 h], long [≥ 9 h], and recommended [> 6 to < 9 h) and self-reported sleep disturbance (yes, no). Multivariable logistic regression models explored the associations between sleep duration, sleep disturbance, and CVD biomarkers adjusting for sociodemographic characteristics and lifestyle behaviors.

Results

The mean sleep duration was 7.1 ± 1.5 h and 25.1% of participants reported sleep disturbances. Compared to participants with the recommended sleep duration, those with short sleep duration had higher odds of abnormal levels of HDL (adjusted odds ratio [aOR] = 1.20, 95% confidence interval [CI] = 1.05–1.39), CRP (aOR = 3.08, 95% CI = 1.18–8.05), HbA1c (aOR = 1.25, 95% CI = 1.05–1.49), and insulin (aOR = 1.24, 95% CI = 1.03–1.51). Long sleep duration was associated with increased odds of abnormal CRP (aOR = 6.12, 95% CI = 2.19–17.15), HbA1c (aOR = 1.54, 95% CI = 1.09–2.17), and blood glucose levels (aOR = 1.45, 95% CI = 1.07–1.95). Sleep disturbance predicted abnormal triglyceride (aOR = 1.18, 95% CI = 1.01–1.37) and blood glucose levels (aOR = 1.24, 95% CI = 1.04–1.49).

Conclusion

Short and long sleep durations were positively associated with abnormal CRP, HDL, HbA1c, blood glucose, and insulin levels, while sleep disturbance was associated with abnormal triglyceride and blood glucose levels. Since sleep is a modifiable factor, adopting healthy sleeping habits may create a balanced metabolism and reduce the risk of developing a CVD. Our study may provide insights into the relationship between sleep duration, sleep disturbance, and CVD risk.
Association of relative hand grip strength with myocardial infarction and angina pectoris in the Korean population: a large-scale cross-sectional study
Authors: Chi Jeong Hee , Lee Bum Ju
Published: April 2024

Background

Low hand grip strength (HGS) is associated with the risk of cardiovascular diseases, but the association between HGS and myocardial infarction/angina pectoris (MIAP) is unclear. Furthermore, there have been no studies examining the associations of MIAP with anthropometric indices, absolute HGS indices, and relative HGS indices calculated by dividing absolute HGS values by body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), or weight values. Therefore, the objective of this study was to examine the associations of MIAP with absolute and relative HGS combined with several anthropometric indices.

Methods

In this large-scale cross-sectional study, a total of 12,963 subjects from the National Health and Nutrition Examination Survey were included. Odds ratios and 95% confidence intervals for the associations of MIAP with anthropometric indices, absolute HGS indices, and relative HGS indices were computed from binary logistic regression models. We built 3 models: a crude model, a model that was adjusted for age (Model 1), and a model that was adjusted for other relevant covariates (Model 2).

Results

For men, the average age was 61.55 ± 0.16 years in the MIAP group and 66.49 ± 0.61 years in the non-MIAP group. For women, the average age was 61.99 ± 0.14 years in the MIAP group and 70.48 ± 0.61 years in the non-MIAP group. For both sexes, the MIAP group had lower diastolic blood pressure, shorter stature, greater WC, and a greater WHtR than did the non-MIAP group, and women tended to have greater systolic blood pressure, weight, and BMI than in men. HGS was strongly associated with the risk of MIAP in the Korean population. In men, relative HGS indices combined with WC and the WHtR had greater associations with MIAP than did the anthropometric indices and absolute HGS indices. However, in women, anthropometric indices, including weight, BMI, WC, and WHtR, were more strongly associated with MIAP than were absolute and relative HGS indices, unlike in men. When comparing absolute and relative HGS indices in women, relative HGS indices combined with BMI and weight was more strongly related to MIAP than was absolute HGS indices.

Conclusions

MIAP might be better identified by relative HGS than absolute HGS in both sexes. The overall magnitudes of the associations of MIAP with absolute and relative HGS are greater in men than in women.
A paradigm shift in cancer research based on integrative multi-omics approaches: glutaminase serves as a pioneering cuproptosis-related gene in pan-cancer
Authors: Shi Hai-hong , Mugaanyi Joseph , Lu Changjiang , Li Yang , Huang Jing , Dai Lei
Published: April 2024

Background

Cuproptosis is a newly identified form of unprogrammed cell death. As a pivotal metabolic regulator, glutaminase (GLS) has recently been discovered to be linked to cuproptosis. Despite this discovery, the oncogenic functions and mechanisms of GLS in various cancers are still not fully understood.

Methods

In this study, a comprehensive omics analysis was performed to investigate the differential expression levels, diagnostic and prognostic potential, correlation with tumor immune infiltration, genetic alterations, and drug sensitivity of GLS across multiple malignancies.

Results

Our findings revealed unique expression patterns of GLS across various cancer types and molecular subtypes of carcinomas, underscoring its pivotal role primarily in energy and nutrition metabolism. Additionally, GLS showed remarkable diagnostic and prognostic performance in specific cancers, suggesting its potential as a promising biomarker for cancer detection and prognosis. Furthermore, we focused on uterine corpus endometrial carcinoma (UCEC) and developed a novel prognostic model associated with GLS, indicating a close correlation between GLS and UCEC. Moreover, our exploration into immune infiltration, genetic heterogeneity, tumor stemness, and drug sensitivity provided novel insights and directions for future research and laid the foundation for high-quality verification.

Conclusion

Collectively, our study is the first comprehensive investigation of the biological and clinical significance of GLS in pan-cancer. In our study, GLS was identified as a promising biomarker for UCEC, providing valuable evidence and a potential target for anti-tumor therapy. Overall, our findings shed light on the multifaceted functions of GLS in cancer and offer new avenues for further research.
Professional values education for undergraduate nursing students: developing a framework based on the professional values growth theory
Authors: Li Jialin , Li Xiaohan
Published: April 2024

Background

Education has been recognised as necessary in forming and internalising professional values. The system and instructors' content in existing educational institutions focus on developing students' knowledge, skills and practices. Still, the development of values has yet to achieve significant effects, leading to a crisis in students' professional identity.

Aims

To construct a professional values growth theory for undergraduate nursing students and develop a corresponding education framework.

Methods

Through the review, some databases(PubMed、CINAHL、Web of Science、Wiley and Google Scholars)were searched using a systematic search strategy to collect relevant literature on professional values education. Based on the nursing professional values growth theory (Li and Li, Nursing Ethics In press, 2022), a theory of professional values growth of nursing undergraduates was developed using the method of theory derivation. Two rounds of expert meetings were conducted to review and revise an education framework of professional values of nursing undergraduates derived from that theory.

Findings

A total of 10 studies were included. The contents of two themes were analysed: theories and models and the current status of the professional values development of nursing students. The resulting professional values growth theory for undergraduate nursing students consists of five parts: key aspects, decisive opportunities, drivers, embodiment (humanistic sentiments, moral emotions), and outcomes. A total of five experts in the relevant fields were invited to this study. After two rounds of expert meetings, an education framework for undergraduate nursing students was finally developed, which consists of four parts: education objectives, education process and content, environment and conditions, and evaluation.

Conclusion

The education framework developed in this study has practical implications for the development of professional values of undergraduate nursing students, providing educational strategies and methods for the growth and internalisation of professional values of undergraduate nursing students.
The use of medical health applications by primary care physicians in Israel: a cross-sectional study
Authors: Amran Menashe Meni , Bilitzky Avital , Bar-Yishay Mattan , Adler Limor
Published: April 2024

Background

The use of medical health applications (mHealth apps) by patients, caregivers, and physicians is widespread. mHealth apps are often employed by physicians to quickly access professional knowledge, guide treatment, easily retrieve medical records, and monitor and manage patients. This study sought to characterize the use of mHealth apps among primary care physicians (PCPs) in Israel. The reasons for using apps and barriers to their use were also investigated.

Methods

From all MHS’ PCPs, we randomly selected 700 PCPs and invited them to complete a questionnaire regarding the use of mHealth apps and attitudes toward them.

Results

From August 2020 to December 2020, 191 physicians completed the questionnaire (response rate 27.3%). 68.0% of PCPs reported using mHealth apps. Telemedicine service apps were the most frequently used. Medical calculators (used for clinical scoring) and differential diagnosis apps were the least frequently used. The most common reason for mHealth app use was accessibility, followed by time saved and a sense of information reliability. Among infrequent users of apps, the most common barriers reported were unfamiliarity with relevant apps and preference for using a computer. Concerns regarding information reliability were rarely reported by PCPs. Physician gender and seniority were not related to mHealth app use. Physician age was related to the use of mHealth apps.

Conclusions

mHealth apps are widely used by PCPs in this study, regardless of physician gender or seniority. Information from mHealth apps is considered reliable by PCPs. The main barrier to app use is unfamiliarity with relevant apps and preference for computer use.
The effect of hyperlipidemia and body fat distribution on subclinical left ventricular function in obesity: a cardiovascular magnetic resonance study
Authors: Liu Jing , Li Jing , Xia Chunchao , He Wenzhang , Li Xue , Shen Sumin , Zhou Xiaoyue , Tong Nanwei , Peng Liqing
Published: April 2024

Background

Obesity is often associated with multiple comorbidities. However, whether obese subjects with hyperlipidemia in the absence of other complications have worse cardiac indices than metabolically healthy obese subjects is unclear. Therefore, we aimed to determine the effect of hyperlipidemia on subclinical left ventricular (LV) function in obesity and to evaluate the association of cardiac parameters with body fat distribution.

Materials and methods

Ninety-two adults were recruited and divided into 3 groups: obesity with hyperlipidemia (n = 24, 14 males), obesity without hyperlipidemia (n = 25, 13 males), and c ntrols (n = 43, 25 males). LV strain parameters (peak strain (PS), peak diastolic strain rate (PDSR), peak systolic strain rate) derived from cardiovascular magnetic resonance tissue tracking were measured and compared. Dual-energy X-ray absorptiometer was used to measure body fat distribution. Correlations of hyperlipidemia and body fat distribution with LV strain were assessed by multivariable linear regression.

Results

Obese individuals with preserved LV ejection fraction showed lower global LV longitudinal, circumferential, and radial PS and longitudinal and circumferential PDSR than controls (all P < 0.05). Among obese patients, those with hyperlipidemia had lower longitudinal PS and PDSR and circumferential PDSR than those without hyperlipidemia (− 12.8 ± 2.9% vs. − 14.2 ± 2.7%, 0.8 ± 0.1 s−1 vs. 0.9 ± 0.3 s−1, 1.2 ± 0.2 s−1 vs. 1.4 ± 0.2 s−1; all P < 0.05). Multivariable linear regression demonstrated that hyperlipidemia was independently associated with circumferential PDSR (β = − 0.477, P < 0.05) in obesity after controlling for growth differences, other cardiovascular risk factors, and central fat distribution. In addition, android fat had an independently negative relationship with longitudinal and radial PS (β = − 0.486 and β = − 0.408, respectively; all P < 0.05); and visceral fat was negatively associated with longitudinal PDSR (β = − 0.563, P < 0.05). Differently, gynoid fat was positively correlated with circumferential PS and PDSR and radial PDSR (β = 0.490, β = 0.481, and β = 0.413, respectively; all P < 0.05).

Conclusion

Hyperlipidemia is independently associated with subclinical LV diastolic dysfunction in obesity. Central fat distribution (android and visceral fat) has a negative association, while peripheral fat distribution (gynoid fat) has a positive association on subclinical LV function. These results suggest that appropriate management of hyperlipidemia may be beneficial for obese patients, and that the differentiation of fat distribution in different regions may facilitate the precise management of obese patients.

Clinical trials registration Effect of lifestyle intervention on metabolism of obese patients based on smart phone software (ChiCTR1900026476).
A deep learning framework for identifying and segmenting three vessels in fetal heart ultrasound images
Authors: Yan Laifa , Ling Shan , Mao Rongsong , Xi Haoran , Wang Fei
Published: April 2024

Background

Congenital heart disease (CHD) is one of the most common birth defects in the world. It is the leading cause of infant mortality, necessitating an early diagnosis for timely intervention. Prenatal screening using ultrasound is the primary method for CHD detection. However, its effectiveness is heavily reliant on the expertise of physicians, leading to subjective interpretations and potential underdiagnosis. Therefore, a method for automatic analysis of fetal cardiac ultrasound images is highly desired to assist an objective and effective CHD diagnosis.

Method

In this study, we propose a deep learning-based framework for the identification and segmentation of the three vessels—the pulmonary artery, aorta, and superior vena cava—in the ultrasound three vessel view (3VV) of the fetal heart. In the first stage of the framework, the object detection model Yolov5 is employed to identify the three vessels and localize the Region of Interest (ROI) within the original full-sized ultrasound images. Subsequently, a modified Deeplabv3 equipped with our novel AMFF (Attentional Multi-scale Feature Fusion) module is applied in the second stage to segment the three vessels within the cropped ROI images.

Results

We evaluated our method with a dataset consisting of 511 fetal heart 3VV images. Compared to existing models, our framework exhibits superior performance in the segmentation of all the three vessels, demonstrating the Dice coefficients of 85.55%, 89.12%, and 77.54% for PA, Ao and SVC respectively.

Conclusions

Our experimental results show that our proposed framework can automatically and accurately detect and segment the three vessels in fetal heart 3VV images. This method has the potential to assist sonographers in enhancing the precision of vessel assessment during fetal heart examinations.
Advances in management of metabolic dysfunction-associated steatotic liver disease: from mechanisms to therapeutics
Authors: Jiang Yuxiao , Wu Lili , Zhu Xiaopeng , Bian Hua , Gao Xin , Xia Mingfeng
Published: April 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease that affects over 30% of the world’s population. For decades, the heterogeneity of non-alcoholic fatty liver disease (NAFLD) has impeded our understanding of the disease mechanism and the development of effective medications. However, a recent change in the nomenclature from NAFLD to MASLD emphasizes the critical role of systemic metabolic dysfunction in the pathophysiology of this disease and therefore promotes the progress in the pharmaceutical treatment of MASLD. In this review, we focus on the mechanism underlying the abnormality of hepatic lipid metabolism in patients with MASLD, and summarize the latest progress in the therapeutic medications of MASLD that target metabolic disorders.
TRAF6-mediated ubiquitination of AKT in the nucleus is a critical event underlying the desensitization of G protein-coupled receptors
Authors: Wu Chengyan , Hu Li , Liu Bing , Zeng Xingyue , Ma Haixiang , Cao Yongkai , Li Huijun , Zhang Xiaohan
Published: April 2024

Background

Desensitization of G protein–coupled receptors (GPCRs) refers to the attenuation of receptor responsiveness by prolonged or intermittent exposure to agonists. The binding of β-arrestin to the cytoplasmic cavity of the phosphorylated receptor, which competes with the G protein, has been widely accepted as an extensive model for explaining GPCRs desensitization. However, studies on various GPCRs, including dopamine D2-like receptors (D2R, D3R, D4R), have suggested the existence of other desensitization mechanisms. The present study employed D2R/D3R variants with different desensitization properties and utilized loss-of-function approaches to uncover the mechanisms underlying GPCRs homologous desensitization, focusing on the signaling cascade that regulates the ubiquitination of AKT.

Results

AKT undergoes K8/14 ubiquitination by TRAF6, which occurs in the nucleus and promotes its membrane recruitment, phosphorylation and activation under receptor desensitization conditions. The nuclear entry of TRAF6 relies on the presence of the importin complex. Src regulates the nuclear entry of TRAF6 by mediating the interaction between TRAF6 and importin β1. Ubiquitinated AKT translocates to the plasma membrane where it associates with Mdm2 to phosphorylate it at the S166 and S186 residues. Thereafter, phosphorylated Mdm2 is recruited to the nucleus, resulting in the deubiquitination of β-Arr2. The deubiquitinated β-Arr2 then forms a complex with Gβγ, which serves as a biomarker for GPCRs desensitization. Like in D3R, ubiquitination of AKT is also involved in the desensitization of β2 adrenoceptors.

Conclusion

Our study proposed that the property of a receptor that causes a change in the subcellular localization of TRAF6 from the cytoplasm to the nucleus to mediate AKT ubiquitination could initiate the desensitization of GPCRs.
EP300-ZNF384 transactivates IL3RA to promote the progression of B-cell acute lymphoblastic leukemia
Authors: Hou Zhijie , Ren Yifei , Zhang Xuehong , Huang Dan , Yan Fanzhi , Sun Wentao , Zhang Wenjuan , Zhang Qingqing , Fu Xihui , Lang Zhenghui , Chu Chenyang , Zou Boyang , Gao Beibei , Jin Bilian , Kang Zhijie , Liu Quentin , Yan Jinsong
Published: April 2024

The EP300-ZNF384 fusion gene is an oncogenic driver in B-cell acute lymphoblastic leukemia (B-ALL). In the present study, we demonstrated that EP300-ZNF384 substantially induces the transcription of IL3RA and the expression of IL3Rα (CD123) on B-ALL cell membranes. Interleukin 3 (IL-3) supplementation promotes the proliferation of EP300-ZNF348-positive B-ALL cells by activating STAT5. Conditional knockdown of IL3RA in EP300-ZF384-positive cells inhibited the proliferation in vitro, and induced a significant increase in overall survival of mice, which is attributed to impaired propagation ability of leukemia cells. Mechanistically, the EP300-ZNF384 fusion protein transactivates the promoter activity of IL3RA by binding to an A-rich sequence localized at -222/-234 of IL3RA. Furthermore, forced EP300-ZNF384 expression induces the expression of IL3Rα on cell membranes and the secretion of IL-3 in CD19-positive B precursor cells derived from healthy individuals. Doxorubicin displayed a selective killing of EP300-ZNF384-positive B-ALL cells in vitro and in vivo. Collectively, we identify IL3RA as a direct downstream target of EP300-ZNF384, suggesting CD123 is a potent biomarker for EP300-ZNF384-driven B-ALL. Targeting CD123 may be a novel therapeutic approach to EP300-ZNF384-positive patients, alternative or, more likely, complementary to standard chemotherapy regimen in clinical setting.
Inefficient antiviral response in reconstituted small-airway epithelium from chronic obstructive pulmonary disease patients following human parainfluenza virus type 3 infection
Authors: Bondeelle Louise , Salmona Maud , Houdouin Véronique , Diaz Elise , Dutrieux Jacques , Mercier-Delarue Séverine , Constant Samuel , Huang Song , Bergeron Anne , LeGoff Jérôme
Published: April 2024

Chronic obstructive pulmonary disease (COPD) affects over 250 million individuals globally and stands as the third leading cause of mortality. Respiratory viral infections serve as the primary drivers of acute exacerbations, hastening the decline in lung function and worsening the prognosis. Notably, Human Parainfluenza Virus type 3 (HPIV-3) is responsible for COPD exacerbations with a frequency comparable to that of Respiratory Syncytial Virus and Influenza viruses. However, the impact of HPIV-3 on respiratory epithelium within the context of COPD remains uncharacterized.

In this study, we employed in vitro reconstitution of lower airway epithelia from lung tissues sourced from healthy donors (n = 4) and COPD patients (n = 5), maintained under air–liquid interface conditions. Through a next-generation sequencing-based transcriptome analysis, we compared the cellular response to HPIV-3 infection.

Prior to infection, COPD respiratory epithelia exhibited a pro-inflammatory profile, notably enriched in canonical pathways linked to antiviral response, B cell signaling, IL-17 signaling, and epithelial-mesenchymal transition, in contrast to non-COPD epithelia. Intriguingly, post HPIV-3 infection, only non-COPD epithelia exhibited significant enrichment in interferon signaling, pattern recognition receptors of viruses and bacteria, and other pathways involved in antiviral responses. This deficiency could potentially hinder immune cell recruitment essential for controlling viral infections, thus fostering prolonged viral presence and persistent inflammation.
[1-11C]-Butanol Positron Emission Tomography reveals an impaired brain to nasal turbinates pathway in aging amyloid positive subjects
Authors: Mehta Neel H. , Wang Xiuyuan , Keil Samantha A. , Xi Ke , Zhou Liangdong , Lee Kevin , Tan Wanbin , Spector Edward , Goldan Amirhossein , Kelly James , Karakatsanis Nicolas A. , Mozley P. David , Nehmeh Sadek , Chazen J. Levi , Morin Simon , Babich John , Ivanidze Jana , Pahlajani Silky , Tanzi Emily B. , Saint-Louis Leslie , Butler Tracy , Chen Kewei , Rusinek Henry , Carare Roxana O. , Li Yi , Chiang Gloria C. , de Leon Mony J.
Published: April 2024

Background

Reduced clearance of cerebrospinal fluid (CSF) has been suggested as a pathological feature of Alzheimer’s disease (AD). With extensive documentation in non-human mammals and contradictory human neuroimaging data it remains unknown whether the nasal mucosa is a CSF drainage site in humans. Here, we used dynamic PET with [1-11C]-Butanol, a highly permeable radiotracer with no appreciable brain binding, to test the hypothesis that tracer drainage from the nasal pathway reflects CSF drainage from brain. As a test of the hypothesis, we examined whether brain and nasal fluid drainage times were correlated and affected by brain amyloid.

Methods

24 cognitively normal subjects (≥ 65 years) were dynamically PET imaged for 60 min. using [1-11C]-Butanol. Imaging with either [11C]-PiB or [18F]-FBB identified 8 amyloid PET positive (Aβ+) and 16 Aβ- subjects. MRI-determined regions of interest (ROI) included: the carotid artery, the lateral orbitofrontal (LOF) brain, the cribriform plate, and an All-turbinate region comprised of the superior, middle, and inferior turbinates. The bilateral temporalis muscle and jugular veins served as control regions. Regional time-activity were used to model tracer influx, egress, and AUC.

Results

LOF and All-turbinate 60 min AUC were positively associated, thus suggesting a connection between the brain and the nose. Further, the Aβ+ subgroup demonstrated impaired tracer kinetics, marked by reduced tracer influx and slower egress.

Conclusion

The data show that tracer kinetics for brain and nasal turbinates are related to each other and both reflect the amyloid status of the brain. As such, these data add to evidence that the nasal pathway is a potential CSF drainage site in humans. These data warrant further investigation of brain and nasal contributions to protein clearance in neurodegenerative disease.
Clinical efficacy of intraoral ultrasonography versus transgingival probing for measurement of gingival thickness in different gingival biotypes: a clinical trial
Authors: Alizad-Rahvar Maryam , Safi Yaser , Kadkhodazadeh Mahdi , Ghomashi Mohammad Parham
Published: April 2024

Background

Transgingival probing is conventionally used for gingival thickness (GT) measurement. However, invasiveness is a major drawback of transgingival probing. Thus, researchers have been in search of alternative methods for measurement of GT. This study compared the clinical efficacy of intraoral ultrasonography and transgingival probing for measurement of GT in different biotypes.

Materials and methods

This clinical trial was conducted on 34 patients requiring crown lengthening surgery. GT was measured at 40 points with 2- and 4-mm distances from the free gingival margin (FGM) of anterior and premolar teeth of both jaws in each patient by an intraoral ultrasound probe. For measurement of GT by the transgingival probing method, infiltration anesthesia was induced, and a #25 finger spreader (25 mm) was vertically inserted into the soft tissue until contacting bone. The inserted length was measured by a digital caliper with 0.01 mm accuracy. All measurements were made by an operator with high reliability under the supervision of a radiologist. Data were analyzed by t-test, Power and Effect Size formula, and intraclass correlation coefficient (ICC).

Results

The two methods were significantly different in measurement of GT in both thick and thin biotypes at 2- and 4-mm distances (P < 0.001). The two methods had a significant difference in both the mandible (P < 0.001) and maxilla (P < 0.001) and in both the anterior (P < 0.003) and premolar (P < 0.003) regions. Although the difference was statistically significant in t-tests, the power and effect formula proved it to be clinically insignificant. Also, the ICC of the two methods revealed excellent agreement.

Conclusion

The results showed optimal agreement of ultrasound and transgingival probing for measurement of GT.

Trial registration

The study was approved by the ethics committee of Shahid Beheshti University of Medical Sciences on 2021-12-28 (IR.SBMU.DRC.REC.1400.138) and registered in the Iranian Registry of Clinical Trials on 2022-03-14 (IRCT20211229053566N1).
Synaptopodin is required for long-term depression at Schaffer collateral-CA1 synapses
Authors: Inglebert Yanis , Wu Pei You , Tourbina-Kolomiets Julia , Dang Cong Loc , McKinney R. Anne
Published: April 2024

Synaptopodin (SP), an actin-associated protein found in telencephalic neurons, affects activity-dependant synaptic plasticity and dynamic changes of dendritic spines. While being required for long-term depression (LTD) mediated by metabotropic glutamate receptor (mGluR-LTD), little is known about its role in other forms of LTD induced by low frequency stimulation (LFS-LTD) or spike-timing dependent plasticity (STDP). Using electrophysiology in ex vivo hippocampal slices from SP-deficient mice (SPKO), we show that absence of SP is associated with a deficit of LTD at Sc-CA1 synapses induced by LFS-LTD and STDP. As LTD is known to require AMPA- receptors internalization and IP3-receptors calcium signaling, we tested by western blotting and immunochemistry if there were changes in their expression which we found to be reduced. While we were not able to induce LTD, long-term potentiation (LTP), albeit diminished in SPKO, can be recovered by using a stronger stimulation protocol. In SPKO we found no differences in NMDAR, which are the primary site of calcium signalling to induce LTP. Our study shows, for the first time, the key role of the requirement of SP to allow induction of activity-dependant LTD at Sc-CA1 synapses.
Nanoparticles in tumor microenvironment remodeling and cancer immunotherapy
Authors: Lu Qiang , Kou Dongquan , Lou Shenghan , Ashrafizadeh Milad , Aref Amir Reza , Canadas Israel , Tian Yu , Niu Xiaojia , Wang Yuzhuo , Torabian Pedram , Wang Lingzhi , Sethi Gautam , Tergaonkar Vinay , Tay Franklin , Yuan Zhennan , Han Peng
Published: April 2024

Cancer immunotherapy and vaccine development have significantly improved the fight against cancers. Despite these advancements, challenges remain, particularly in the clinical delivery of immunomodulatory compounds. The tumor microenvironment (TME), comprising macrophages, fibroblasts, and immune cells, plays a crucial role in immune response modulation. Nanoparticles, engineered to reshape the TME, have shown promising results in enhancing immunotherapy by facilitating targeted delivery and immune modulation. These nanoparticles can suppress fibroblast activation, promote M1 macrophage polarization, aid dendritic cell maturation, and encourage T cell infiltration. Biomimetic nanoparticles further enhance immunotherapy by increasing the internalization of immunomodulatory agents in immune cells such as dendritic cells. Moreover, exosomes, whether naturally secreted by cells in the body or bioengineered, have been explored to regulate the TME and immune-related cells to affect cancer immunotherapy. Stimuli-responsive nanocarriers, activated by pH, redox, and light conditions, exhibit the potential to accelerate immunotherapy. The co-application of nanoparticles with immune checkpoint inhibitors is an emerging strategy to boost anti-tumor immunity. With their ability to induce long-term immunity, nanoarchitectures are promising structures in vaccine development. This review underscores the critical role of nanoparticles in overcoming current challenges and driving the advancement of cancer immunotherapy and TME modification.
LncRNA SNHG12 promotes cell proliferation and inhibits apoptosis of granulosa cells in polycystic ovarian syndrome by sponging miR-129 and miR-125b
Authors: Xuan Feilan , Jin Ruiying , Zhou Weimei , Ye Yongju , Ren Yuefang , Lu Jiali , Chen Aixue
Published: April 2024

Background

Polycystic ovarian syndrome (PCOS) is the most common endocrine disease in women of childbearing age which is often associated with abnormal proliferation or apoptosis of granulosa cells (GCs). Studies proved that long non-coding RNA SNHG12 (lncRNA SNHG12) is significantly increased in ovarian cancer and cervical cancer patients and cells. The inhibition of lncRNA SNHG12 restrains the proliferation, migration, and invasion in tumor cells.

Objective

This study explores the role of lncRNA SNHG12 in the apoptosis of GCs in PCOS and the underlying regulated mechanism.

Methods

In this study, the injection of dehydroepiandrosterone (DHEA) successfully induced the PCOS model in SD rats. The human granulosa-like tumor cell line KGN was incubated with insulin to assess the effects of lncRNA SNHG12 on GC proliferation and apoptosis.

Results

Overexpression of lncRNA SNHG12 influenced the body weight, ovary weight, gonadal hormone, and pathological changes, restrained the expressions of microRNA (miR)-129 and miR-125b, while downregulation of lncRNA SNHG12 exerted the opposite effects in PCOS rats. After silencing lncRNA SNHG12 in cells, the cell viability and proliferation were lessened whereas apoptosis of cells was increased. A loss-of-functions test was implemented by co-transfecting miR-129 and miR-125b inhibitors into lncRNA SNHG12-knocking down cells to analyze the effects on cell viability and apoptosis. Next, the existence of binding sites of SNHG12 and miR-129/miR-125b was proved based on the pull-down assay.

Conclusion

lncRNA SNHG12 might be a potential regulatory factor for the development of PCOS by sponging miR-129 and miR-125b in GCs.
Non-technical skills needed by medical disaster responders– a scoping review
Authors: Westman Anja , Kurland Lisa , Hugelius Karin
Published: April 2024

Background

There is no universal agreement on what competence in disaster medicine is, nor what competences and personal attributes add value for disaster responders. Some studies suggest that disaster responders need not only technical skills but also non-technical skills. Consensus of which non-technical skills are needed and how training for these can be provided is lacking, and little is known about how to apply knowledge of non-technical skills in the recruitment of disaster responders. Therefore, this scoping review aimed to identify the non-technical skills required for the disaster medicine response.

Method

A scooping review using the Arksey & O´Malley framework was performed. Structured searches in the databases PuBMed, CINAHL Full Plus, Web of Science, PsycInfo and Scopus was conducted. Thereafter, data were structured and analyzed.

Results

From an initial search result of 6447 articles, 34 articles were included in the study. These covered both quantitative and qualitative studies and different contexts, including real events and training. The most often studied real event were responses following earthquakes. Four non-technical skills stood out as most frequently mentioned: communication skills; situational awareness; knowledge of human resources and organization and coordination skills; decision-making, critical-thinking and problem-solving skills. The review also showed a significant lack of uniform use of terms like skills or competence in the reviewed articles.

Conclusion

Non-technical skills are skills that disaster responders need. Which non-technical skills are most needed, how to train and measure non-technical skills, and how to implement non-technical skills in disaster medicine need further studies.
Regulatory mechanisms of autophagy on DHA and carotenoid accumulation in Crypthecodinium sp. SUN
Authors: Li Yiming , Zhao Tiantian , Gao Weizheng , Miao Bowen , Fu Zhongxiang , Zhang Zhao , Li Qingyang , Sun Dongzhe
Published: April 2024

Background

Autophagy is a crucial process of cellular self-destruction and component reutilization that can affect the accumulation of total fatty acids (TFAs) and carotenoids in microalgae. The regulatory effects of autophagy process in a docosahexaenoic acid (DHA) and carotenoids simultaneously producing microalga, Crypthecodinium sp. SUN, has not been studied. Thus, the autophagy inhibitor (3-methyladenine (MA)) and activator (rapamycin) were used to regulate autophagy in Crypthecodinium sp. SUN.

Results

The inhibition of autophagy by 3-MA was verified by transmission electron microscopy, with fewer autophagy vacuoles observed. Besides, 3-MA reduced the glucose absorption and intracellular acetyl-CoA level, which resulting in the decrease of TFA and DHA levels by 15.83 and 26.73% respectively; Surprisingly, 3-MA increased intracellular reactive oxygen species level but decreased the carotenoids level. Comparative transcriptome analysis showed that the downregulation of the glycolysis, pentose phosphate pathway and tricarboxylic acid cycle may underlie the decrease of acetyl-CoA, NADPH and ATP supply for fatty acid biosynthesis; the downregulation of PSY and HMGCR may underlie the decreased carotenoids level. In addition, the class I PI3K-AKT signaling pathway may be crucial for the regulation of carbon and energy metabolism. At last, rapamycin was used to activate autophagy, which significantly enhanced the cell growth and TFA level and eventually resulted in 1.70-fold increase in DHA content.

Conclusions

Our findings indicate the mechanisms of autophagy in Crypthecodinium sp. SUN and highlight a way to manipulate cell metabolism by regulating autophagy. Overall, this study provides valuable insights to guide further research on autophagy-regulated TFA and carotenoids accumulation in Crypthecodinium sp. SUN.