bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of mitochondrial dynamics and mitophagy in skeletal muscle atrophy: from molecular mechanisms to therapeutic insights
Authors: Lei Yuhang , Gan Mailin , Qiu Yanhao , Chen Qiuyang , Wang Xingyu , Liao Tianci , Zhao Mengying , Chen Lei , Zhang Shunhua , Zhao Ye , Niu Lili , Wang Yan , Zhu Li , Shen Linyuan
Published: April 2024

Skeletal muscle is the largest metabolic organ of the human body. Maintaining the best quality control and functional integrity of mitochondria is essential for the health of skeletal muscle. However, mitochondrial dysfunction characterized by mitochondrial dynamic imbalance and mitophagy disruption can lead to varying degrees of muscle atrophy, but the underlying mechanism of action is still unclear. Although mitochondrial dynamics and mitophagy are two different mitochondrial quality control mechanisms, a large amount of evidence has indicated that they are interrelated and mutually regulated. The former maintains the balance of the mitochondrial network, eliminates damaged or aged mitochondria, and enables cells to survive normally. The latter degrades damaged or aged mitochondria through the lysosomal pathway, ensuring cellular functional health and metabolic homeostasis. Skeletal muscle atrophy is considered an urgent global health issue. Understanding and gaining knowledge about muscle atrophy caused by mitochondrial dysfunction, particularly focusing on mitochondrial dynamics and mitochondrial autophagy, can greatly contribute to the prevention and treatment of muscle atrophy. In this review, we critically summarize the recent research progress on mitochondrial dynamics and mitophagy in skeletal muscle atrophy, and expound on the intrinsic molecular mechanism of skeletal muscle atrophy caused by mitochondrial dynamics and mitophagy. Importantly, we emphasize the potential of targeting mitochondrial dynamics and mitophagy as therapeutic strategies for the prevention and treatment of muscle atrophy, including pharmacological treatment and exercise therapy, and summarize effective methods for the treatment of skeletal muscle atrophy.
Associations between maternal blood metal concentrations during the first trimester and spontaneous preterm birth: a nested case-control study
Authors: Wu Zhengqin , Cao Hua , Wang Xinrui , Miao Chong , Li Haibo , Sun Bin , Gao Haiyan , Liu Wenjuan , Li Wei , Zhu Yibing
Published: April 2024

Background

Few studies have utilized whole blood samples to investigate the association between metal mixture exposure during early pregnancy and spontaneous preterm birth (SPB). We conduct this nested case–control study to investigate both the independent and joint effect of each metal, and identify critical metals in the metal mixture.

Results

A total of 120 pregnant women with SPB and 120 pregnant women with full-term delivery were selected from the prospective birth cohort. We measured 14 metal concentrations in maternal blood collected during 10–13 weeks gestation. Conditional logistic regression showed that high concentrations of vanadium (V), magnesium, and copper were positively associated with SPB (Adjusted OR = 5.76 (95% CI 2.46–13.53), 3.64 (95% CI 1.64–8.09), 2.88 (95% CI 1.29–6.41), respectively). Moderate manganese (Mn) concentration (50th–75th percentile) group had the lowest estimated OR (Adjusted OR = 0.32 (95% CI 0.13–0.76)). The high level of strontium (Sr) was negatively associated with SPB (Adjusted OR = 0.39 (95% CI 0.17–0.91)). The BKMR model showed a significant positive joint effect of metal mixture exposure on SPB, while V was the most important metal. The non-linear effects of V and lead (Pb) on SPB, and the interaction effects between V–Pb, Sr–Mn were also revealed.

Conclusions

Maternal blood metal mixtures in the first trimester were found to be positively associated with SPB, with V exhibiting the strongest independent association. Mn had a potential U-shaped association with SPB. Elimination of metal contamination in the environment has a positive impact on maternal and child health.
Purinergic inhibitory regulation of esophageal smooth muscle is mediated by P2Y receptors and ATP-dependent potassium channels in rats
Authors: Shiina Takahiko , Suzuki Yuji , Horii Kazuhiro , Sawamura Tomoya , Yuki Natsufu , Horii Yuuki , Shimizu Yasutake
Published: April 2024

Purines such as ATP are regulatory transmitters in motility of the gastrointestinal tract. The aims of this study were to propose functional roles of purinergic regulation of esophageal motility. An isolated segment of the rat esophagus was placed in an organ bath, and mechanical responses were recorded using a force transducer. Exogenous application of ATP (10–100 μM) evoked relaxation of the esophageal smooth muscle in a longitudinal direction under the condition of carbachol (1 μM) -induced precontraction. Pretreatment with a non-selective P2 receptor antagonist, suramin (500 μM), and a P2Y receptor antagonist, cibacron blue F3GA (200 μM), inhibited the ATP (100 μM) -induced relaxation, but a P2X receptor antagonist, pyridoxal phosphate-6-azophenyl-2,4-disulfonic acid (50 μM), did not affect it. A blocker of ATP-dependent potassium channels (KATP channels), glibenclamide (200 μM), inhibited the ATP-induced relaxation and application of an opener of KATP channels, nicorandil (50 μM), produced relaxation. The findings suggest that ATP is involved in inhibitory regulation of the longitudinal smooth muscle in the muscularis mucosae of the rat esophagus via activation of P2Y receptors and then opening of KATP channels.
Mir-195-5p targets Smad7 regulation of the Wnt/β-catenin pathway to promote osteogenic differentiation of vascular smooth muscle cells
Authors: Lin Wei , Hou Lianglei , Tang Jialyu , Huang Anwu , Jia Zhuyin
Published: April 2024

In this study, we sought to investigate the mechanisms of action of miR-195-5p in the osteogenic differentiation of vascular smooth muscle cells (VSMCs), and thereby provide novel insights and a reference for the targeted therapy of arterial media calcification. VSMC differentiation was induced using sodium β-glycerophosphate, and we investigated the effects of transfecting cells with miR-195-5p mimics, vectors overexpressing Smad7, and the Wnt/β-catenin pathway inhibitor (KYA1797K) on VSMC differentiation by determining cell viability and apoptosis, and the mRNA and protein expression of factors associated with osteogenic differentiation and the Wnt/β-catenin pathway. The results revealed that miR-195-5p mimics enhanced the osteogenic differentiation of VSMCs induced by β-glycerophosphate, whereas the overexpression of Smad7 reversed this phenomenon. In addition, KYA1797K was found to promote the effects of Smad7 overexpression. In conclusion, by targeting, Smad7, miR-195-5p promotes the Wnt/β-catenin pathway. and thus the osteogenic differentiation of VSMCs. These findings will provide a reference for elucidating the mechanisms whereby miR-195-5p regulates osteogenic differentiation.
Imaging segmentation mechanism for rectal tumors using improved U-Net
Authors: Zhang Kenan , Yang Xiaotang , Cui Yanfen , Zhao Jumin , Li Dengao
Published: April 2024

Objective

In radiation therapy, cancerous region segmentation in magnetic resonance images (MRI) is a critical step. For rectal cancer, the automatic segmentation of rectal tumors from an MRI is a great challenge. There are two main shortcomings in existing deep learning-based methods that lead to incorrect segmentation: 1) there are many organs surrounding the rectum, and the shape of some organs is similar to that of rectal tumors; 2) high-level features extracted by conventional neural networks often do not contain enough high-resolution information. Therefore, an improved U-Net segmentation network based on attention mechanisms is proposed to replace the traditional U-Net network.

Methods

The overall framework of the proposed method is based on traditional U-Net. A ResNeSt module was added to extract the overall features, and a shape module was added after the encoder layer. We then combined the outputs of the shape module and the decoder to obtain the results. Moreover, the model used different types of attention mechanisms, so that the network learned information to improve segmentation accuracy.

Results

We validated the effectiveness of the proposed method using 3773 2D MRI datasets from 304 patients. The results showed that the proposed method achieved 0.987, 0.946, 0.897, and 0.899 for Dice, MPA, MioU, and FWIoU, respectively; these values are significantly better than those of other existing methods.

Conclusion

Due to time savings, the proposed method can help radiologists segment rectal tumors effectively and enable them to focus on patients whose cancerous regions are difficult for the network to segment.

Significance

The proposed method can help doctors segment rectal tumors, thereby ensuring good diagnostic quality and accuracy.
The anxiety response of patients with severe psychiatric disorders to the recent public health crisis
Authors: Khalkhali Mohammadrasoul , Zarvandi Parsa , Mohammadpour Mehrshad , Alavi Seyed Mohsen Kheirkhah , Khalkhali Parnian , Farrahi Hassan
Published: April 2024

Background

The devastating health, economic, and social consequences of COVID-19 may harm the already vulnerable groups, particularly people with severe psychiatric disorders (SPDs). The present study was conducted to investigate the anxiety response of patients with SPDs during the COVID-19 pandemic.

Methods

A total of 351 patients with SPDs [Schizophrenia Spectrum (SSD), Bipolar (BD), Major Depressive (MDD), and Obsessive-Compulsive (OCD) Disorders] and healthy controls in Guilan province, Iran, throughout 2021–2022 were included in this cross-sectional analytical study. The anxiety response consisted of four concepts: COVID-19-related anxiety, general health anxiety, anxiety sensitivity, and safety behaviors. We conducted an unstructured interview and provided sociodemographic and clinical information. Also, the participants were asked to complete four self-report measures of the Corona Disease Anxiety Scale, the Anxiety Sensitivity Index–Revised, the Short Health Anxiety Inventory, and the Checklist of Safety Behaviors.

Results

Analysis of variance showed a significant difference between the groups of patients with SPDs and the control group in COVID-19-related anxiety (F = 6.92, p = 0.0001), health anxiety (F = 6.21, p = 0.0001), and safety behaviors (F = 2.52, p = 0.41). No significant difference was observed between them in anxiety sensitivity (F = 1.77, p = 0.134). The Games-Howell test showed that the control group obtained a higher mean than the groups of people with BD (p < 0.0001), SSD (p = 0.033), and OCD (p = 0.003) disorders in COVID-19-related anxiety. The patients with MDD (p = 0.014) and OCD (p = 0.01) had a higher mean score than the control group in health anxiety. Tukey’s test showed that the mean of safety behaviors of the control group was significantly higher than the OCD group (p = 0.21). No significant difference was found between the groups of patients with MDD, BD, SSD, and OCD in terms of COVID-19-related anxiety, health anxiety, and safety behaviors.

Conclusion

Anxiety response to health crisis is different in groups with SPDs and control group. The findings of this study suggest that although health anxiety is present in many of these patients during the pandemic, their anxiety response to the health crisis may be less than expected. There can be various explanations, such as pre-existing symptoms, low health literacy, and possible co-occurring cognitive impairment. The results of this study have many practical and policy implications in meeting the treatment needs of this group of patients during public health crises and indicate that their needs may not be compatible with the expectations and estimates that health professionals and policymakers already have.
Obstructive sleep apnea and mental disorders: a bidirectional mendelian randomization study
Authors: Liu Heming , Wang Xuemei , Feng Hu , Zhou Shengze , Pan Jinhua , Ouyang Changping , Hu Xiaobin
Published: April 2024

Background

Previous studies have reported associations between obstructive sleep apnea (OSA) and several mental disorders. However, further research is required to determine whether these associations are causal. Therefore, we evaluated the bidirectional causality between the genetic liability for OSA and nine mental disorders by using Mendelian randomization (MR).

Method

We performed two-sample bidirectional MR of genetic variants for OSA and nine mental disorders. Summary statistics on OSA and the nine mental disorders were extracted from the FinnGen study and the Psychiatric Genomics Consortium. The primary analytical approach for estimating causal effects was the inverse-variance weighted (IVW), with the weighted median and MR Egger as complementary methods. The MR Egger intercept test, Cochran’s Q test, Rucker’s Q test, and the MR pleiotropy residual sum and outlier (MR-PRESSO) test were used for sensitivity analyses.

Result

MR analyses showed that genetic liability for major depressive disorder (MDD) was associated with an increased risk of OSA (odds ratio [OR] per unit increase in the risk of MDD, 1.29; 95% CI, 1.11–1.49; P < 0.001). In addition, genetic liability for OSA may be associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD) (OR = 1.26; 95% CI, 1.02–1.56; p = 0.032). There was no evidence that OSA is associated with other mental disorders.

Conclusion

Our study indicated that genetic liability for MDD is associated with an increased risk of OSA without a bidirectional relationship. Additionally, there was suggestive evidence that genetic liability for OSA may have a causal effect on ADHD. These findings have implications for prevention and intervention strategies targeting OSA and ADHD. Further research is needed to investigate the biological mechanisms underlying our findings and the relationship between OSA and other mental disorders.
Relationship between self-reported hearing and vision problems, cognitive decline, depressive symptoms, and life satisfaction in older adults: a retrospective observational study
Authors: Chen Yuan
Published: April 2024

Background

Sensory impairment in older adults is associated with cognitive decline, elevated depressive symptoms, and low levels of life satisfaction. However, these relationships are usually investigated separately and in pairs. This study examined these relationships comprehensively, for the first time.

Methods

The analysis included 5,658 community-dwelling older adults from the China Health and Retirement Longitudinal Study (aged 50 to 108 years, 52.1% male) who completed the Jorm Informant Questionnaire Cognitive Decline in the Elderly and the Center for Epidemiological Studies-Depression-short form. A questionnaire was used to collect information on hearing, visual status, and life satisfaction. Structural equation modelling was used to examine the direct and indirect relationships between these variables.

Results

Self-reported hearing and vision problems are directly associated with cognitive decline and elevated depressive symptoms. In addition, hearing and vision problems are indirectly related to cognitive decline through elevated depressive symptoms. Although hearing and vision problems had no direct effect on life satisfaction, they were indirectly associated with life satisfaction through cognitive decline and depressive symptoms.

Conclusions

This study provides the first epidemiological evidence of the comprehensive relationships between hearing and vision problems, cognitive decline, depressive symptoms, and life satisfaction. When older adults report hearing and/or vision problems, clinicians and caregivers should be aware of the concurrence of declined cognition, elevated depressive symptoms, and compensated life satisfaction. Future studies should examine the causal relationships and potential mechanisms of these relationships.
Intraluminal extension of papillary thyroid carcinoma into the Internal Jugular Vein; a case report
Authors: Jafari Firouze , Akerdi Ali Taheri , Fard Hossein Abdolrahimzadeh , karajizadeh Mehrdad , Paydar Shahram
Published: April 2024

Background

Papillary thyroid carcinoma (PTC), being the most common thyroid malignancy, is a slow-growing tumor and is usually limited to the thyroid. Extra thyroid extension is uncommon; besides, invasion to the vasculature seems to be extremely rare and usually indicates aggressive nature of the disease.

Case presentation

We present a case of a 40-year-old lady who referred with a palpable neck mass a month after total thyroidectomy which its histopathologic examination revealed follicular variant of PTC; the same variant as prior thyroidectomy. Preoperative ultrasonography failed to comment on the intravascular component of the mass. Surgical procedure confirmed a mass attaching and infiltrating to the internal jugular vein, which turned out to be persistent disease.

Conclusions

Awareness of this entity is important for surgeons, oncologists and radiologist as it can influence patient management.
Relationship between workplace spirituality with organization-based self-esteem and workplace deviant behaviors among Iranian nurses
Authors: Moez Behzad Sirousi , Sadeghi Amir , Tapak Leili , Purfarzad Zahra
Published: April 2024

Background

Despite the numerous studies conducted on workplace spirituality, there is still lack of studies that have explored the relationship between workplace spirituality with organization-based self-esteem and workplace deviant behaviors. This study aims to examine the relationship between workplace spirituality with organization-based self-esteem and workplace deviant behaviors among Iranian nurses.

Methods

236 nurses from 5 hospitals participated in this descriptive, analytical, and cross-sectional study from August to December 2022. Data was gathered by four questionnaires: demographic information, workplace spirituality, organization-based self-steam, and workplace deviant behaviors. The data were analyzed by SPSS 26 based on descriptive and inferential statistics (Independent Two-sample t Test, Pearson correlation coefficient and multiple regression).

Results

Based on the findings, nurses had a moderate level of perception of workplace spirituality and organization-based self-esteem while having a low level of perception regarding the occurrence of workplace deviate behaviors. Results of Pearson correlation coefficient test showed a positive and statistically significant relationship between workplace spirituality and organization-based self-esteem. Additionally, there was an inverse and significant relationship between workplace spirituality and organization-based self-esteem with workplace deviant behaviors. Results of multiple regression analyses indicate that by controlling the demographic characteristics of nurses, the meaningful work and sense of community have a significant relationship with organization-based self-esteem. Furthermore, by controlling the demographic characteristics of nurses, permanent employment status, sense of community, alignment with the organization’s values, and organization-based self-esteem have a significant relationship with workplace deviant behavior.

Conclusions

The study suggests that organizations must prioritize promoting workplace spirituality and organization-based self-esteem to ensure a healthy work environment and prevent workplace deviant behaviors.
The development of a framework for clinical education programme of undergraduate nursing students in Ghana
Authors: Ti-enkawol Nachinab Gilbert , Armstrong Susan Jennifer
Published: April 2024

Introduction

Clinical education is an important aspect of the training of nursing students but it is faced with challenges in Ghana. The development of a framework will respond to the need for improvement in the quality of clinical nursing education. This study describes part of a larger study which culminated in the development of a framework for a clinical education programme for undergraduate nursing students in Ghana. The aim of the current study was to integrate findings from a scoping review and situational analysis to develop a framework for clinical education in nursing.

Methods

A sequential multimethod design approach was used to conduct the study. A scoping review on the practices that facilitate clinical nursing education and situational analysis were first conducted. The lessons learnt from the scoping review and the situational analysis provided the data matrix that was triangulated to develop the framework. The framework was developed using the model for clinical education developed by South African Nursing Education Stakeholders in consultation with experts in nursing education. An implementation plan was developed from the framework and evaluated using a Delphi technique.

Findings

The resulting framework indicates the need for effective communication and collaboration between nursing education institution and the service setting to ensure that there is a well-structured clinical placement, formal supervision system and effective clinical assessment of students. The framework also proposes that to ensure quality clinical nursing education there is the need for Nursing Education Institutions to implement innovative and cost-effective clinical teaching methods.

Conclusion

The framework spells out the functions of the various stakeholders in nursing education and how these can be integrated and implemented to enhance quality clinical nursing education. Effectiveness of the thematic areas of the framework will increase the quality of clinical nursing education.
A novel multifunctional microneedle patch for synergistic photothermal- gas therapy against maxillofacial malignant melanoma and associated skin defects
Authors: Dong Shaojie , Zhang Yuwei , Zhang Yifei , Mei Yukun , Sina Ahmadi , Zou Rui , Niu Lin
Published: April 2024

Considering the high recrudescence and the long-lasting unhealed large-sized wound that affect the aesthetics and cause dysfunction after resection of maxillofacial malignant skin tumors, a groundbreaking strategy is urgently needed. Photothermal therapy (PTT), which has become a complementary treatment of tumors, however, is powerless in tissue defect regeneration. Therefore, a novel multifunctional sodium nitroprusside and Fe2+ ions loaded microneedles (SNP-Fe@MNs) platform was fabricated by accomplishing desirable NIR-responsive photothermal effect while burst releasing nitric oxide (NO) after the ultraviolet radiation for the ablation of melanoma. Moreover, the steady releasing of NO in the long term by the platform can exert its angiogenic effects via upregulating multiple related pathways to promote tissue regeneration. Thus, the therapeutic dilemma caused by postoperative maxillofacial skin malignancies could be conquered through promoting tumor cell apoptosis via synergistic PTT—gas therapy and subsequent regeneration process in one step. The bio-application of SNP-Fe@MNs could be further popularized based on its ideal bioactivity and appealing features as a strategy for synergistic therapy of other tumors occurred in skin.

Graphical Abstract
Lipoxin A4 analogue, BML-111, reduces platelet activation and protects from thrombosis
Authors: AlOmar Shatha , Mitchell Joanne L , AlZahrani Eman
Published: April 2024

Formyl peptide receptors (FPRs) are members of seven transmembrane G protein-coupled receptors superfamily that exhibit different responses based on the nature of stimulating ligand type. FPRs have been shown to be present in platelets and regulate their function. However, the effect of formyl peptide receptor 2 (FPR2/ALX) lipid ligands on platelets has not yet been addressed. Hence, we sought to study the role of FPR2/ALX ligand and lipoxin A4 lipid analogue, BML-111, in the modulation of platelet function and thrombus formation. Immunofluorescence microscopy showed subcellular distribution and peripheral mobilisation of FPR2/ALX in stimulated platelets. This variation in distribution was further confirmed using flow cytometry. BML-111 inhibited a range of platelet activities in a dose-dependent manner in response to several platelet agonists. This included aggregation, fibrinogen binding to integrin αIIbβ3, α-granule secretion, dense granule secretion, Ca2 + mobilisation and integrin αIIbβ3-mediated outside-in signaling. The selectivity of BML-111 for FPR2/ALX was confirmed using FPR2/ALX deficient mice in flow cytometry assays. In vitro thrombus formation was also inhibited by various concentrations of BML-111. Moreover, the levels of vasodilator stimulated phosphorylation (VASP-S157) increased significantly after BML-111 treatment in resting and stimulated platelets via protein kinase A (PKA) independently of cyclic adenosine monophosphate (cAMP) signaling. Together, our findings demonstrate the significance of BML-111 as a modulator of platelet function via FPR2/ALX and unravel the thrombo-protective potentials of BML-111 induced signaling against thrombo-inflammatory diseases.
Reliability and validity of rapid assessment tools for measuring 24-hour movement behaviours in children aged 0–5 years: the Movement Behaviour Questionnaire Baby (MBQ-B) and child (MBQ-C)
Authors: Trost Stewart G. , Terranova Caroline O. , Brookes Denise S.K. , Chai Li Kheng , Byrne Rebecca A.
Published: April 2024

Background

The development of validated “fit-for-purpose” rapid assessment tools to measure 24-hour movement behaviours in children aged 0–5 years is a research priority. This study evaluated the test-retest reliability and concurrent validity of the open-ended and closed-ended versions of the Movement Behaviour Questionnaire for baby (MBQ-B) and child (MBQ-C).

Methods

300 parent-child dyads completed the 10-day study protocol (MBQ-B: N = 85; MBQ-C: N = 215). To assess validity, children wore an accelerometer on the non-dominant wrist (ActiGraph GT3X+) for 7 days and parents completed 2 × 24-hour time use diaries (TUDs) recording screen time and sleep on two separate days. For babies (i.e., not yet walking), parents completed 2 × 24-hour TUDs recording tummy time, active play, restrained time, screen time, and sleep on days 2 and 5 of the 7-day monitoring period. To assess test-retest reliability, parents were randomised to complete either the open- or closed-ended versions of the MBQ on day 7 and on day 10. Test-retest intraclass correlation coefficients (ICC’s) were calculated using generalized linear mixed models and validity was assessed via Spearman correlations.

Results

Test-retest reliability for the MBQ-B was good to excellent with ICC’s ranging from 0.80 to 0.94 and 0.71–0.93 for the open- and closed-ended versions, respectively. For both versions, significant positive correlations were observed between 24-hour diary and MBQ-B reported tummy time, active play, restrained time, screen time, and sleep (rho = 0.39–0.87). Test-retest reliability for the MBQ-C was moderate to excellent with ICC’s ranging from 0.68 to 0.98 and 0.44–0.97 for the open- and closed-ended versions, respectively. For both the open- and closed-ended versions, significant positive correlations were observed between 24-hour diary and MBQ-C reported screen time and sleep (rho = 0.44–0.86); and between MBQ-C reported and device-measured time in total activity and energetic play (rho = 0.27–0.42).

Conclusions

The MBQ-B and MBQ-C are valid and reliable rapid assessment tools for assessing 24-hour movement behaviours in infants, toddlers, and pre-schoolers. Both the open- and closed-ended versions of the MBQ are suitable for research conducted for policy and practice purposes, including the evaluation of scaled-up early obesity prevention programs.
A randomized clinical trial investigating the impact of magnesium supplementation on clinical and biochemical measures in COVID-19 patients
Authors: Rostami Sepideh , Alavi Seyed Mohammad , Daghagheleh Robab , Maraghi Elham , Hosseini Seyed Ahmad
Published: April 2024

Background

This study sought to examine the impact of magnesium supplementation on clinical outcomes and biochemical factors among hospitalized patients with COVID-19.

Methods

This double-blind, randomized clinical trial was conducted at Razi Hospital, Ahvaz, Iran, between September 2021 and March 2022. Participants aged 18–70 years with moderate disease severity were enrolled. Magnesium supplementation (300 mg daily) was administered to the intervention group, while the control group received a placebo. Clinical outcomes, including the need for oxygen therapy, oxygen saturation, respiratory rate, fever, hs-CRP and TNF-α levels, as well as quality of life and mental health, were assessed. Blood samples were collected to measure biochemical variables.

Results

The main result was the count of individuals requiring oxygen therapy. Additional outcomes comprised of oxygen saturation, respiratory rate, fever, hs-CRP and TNF-α levels, as well as quality of life and mental health. Out of 64 participants, 60 completed the study. The results showed that magnesium supplementation significantly reduced the number of patients requiring oxygen therapy (9 vs. 14; P < 0.001). Moreover, the magnesium group demonstrated improved oxygen saturation compared to the control group (4.55 ± 2.35 vs. 1.8 ± 1.67; P < 0.001). Furthermore, we observed a noteworthy enhancement in the quality of life and depression score in the magnesium group. No significant differences were observed in respiratory rate, fever, hs-CRP, and TNF-α levels (P > 0.05).

Conclusion

The findings suggest that magnesium supplementation may have beneficial effects on clinical outcomes and arterial oxygen saturation in COVID-19 patients. More investigation is necessary to delve into its potential mechanisms and long-term effects on patient outcomes.

Trial registration

This study is registered on Iranian Registry of Clinical Trials (IRCT) under identifier IRCT20210413050957N1. (The registration date: May 1, 2021).
Exploration of treatment in childhood Langerhans cell histiocytosis based on inflammatory and malignant symptoms: a pilot study
Authors: Lin Hui-ling , Zheng Qing-qing , Huang Ru-lin , Hu Rong , Liu Xiao-dan , Wang Jia-yi
Published: April 2024

Background

Multisystem childhood Langerhans cell histiocytosis (LCH) patients, especially those with risk organ (RO) involved, had not been satisfactorily treated under the international traditional schemes as high incidences of reactivation with late sequelae were largely reported. Over years, we have observed that LCH patients with varied clinical symptoms responded differently to different drugs, suggesting the current grouping strategies based only on the number of organs involved might be inadequate. LCH has been defined as an inflammatory myeloid tumor, thus this study has innovatively divided LCH pediatric patients into inflammatory or malignant symptoms group, and given different intensity treatment regimens to different groups.

Aim

This clinical study aimed to explore a more appropriate patient grouping system according to the LCH symptom presentations and examine the clinical outcomes of treatment strategies in different groups.

Methods

According to the clinical manifestations, 37 cases of children were divided into Group A (only inflammatory symptoms) and Group B (malignant symptoms with or without inflammatory symptoms). Patients in Group A and B were initially treated with vindesine (VDS) and methylprednisolone (PSL), and VDS, PSL, pirarubicin (THP) and cyclophosphamide (CTX), respectively. Treatment responses were evaluated six weeks after the induction therapy in all patients, and the criteria were disease status and clinical scores of symptoms.

Results

Pre- and post-treatment scores were 1.22 ± 0.547 and 0.00 ± 0.00 in Group A, and 14.79 ± 1.686 and 1.00 ± 1.563 in Group B, respectively. All patients had subsequentlly received maintenance therapy without progressive disease. The 4-year overall survival (OS) rate was 100% in both groups and the 4-year event-free survival (EFS) was 94.4% in Group A and 89.5% in Group B, respectively. There were no obvious adverse events (AE) in Group A, whereas the main AE in Group B were alopecia and non-lethal hematological toxicity.

Conclusion

Stratification according to patients’ clinical symptoms, with low-intensity treatment for inflammatory symptoms (mild manifestations) and intensive treatment with multiple drugs for malignant symptoms (severe manifestations), is a positive exploration that simplifies stratification method, achieves good long-term remission of the disease, and obtains a higher survival rate and quality of life, which seemed to be more appropriate for LCH patients.
CircCDYL2 bolsters radiotherapy resistance in nasopharyngeal carcinoma by promoting RAD51 translation initiation for enhanced homologous recombination repair
Authors: Qu Hongke , Wang Yumin , Yan Qijia , Fan Chunmei , Zhang Xiangyan , Wang Dan , Guo Can , Chen Pan , Shi Lei , Liao Qianjin , Zhou Ming , Wang Fuyan , Zeng Zhaoyang , Xiang Bo , Xiong Wei
Published: April 2024

Background

Radiation therapy stands to be one of the primary approaches in the clinical treatment of malignant tumors. Nasopharyngeal Carcinoma, a malignancy predominantly treated with radiation therapy, provides an invaluable model for investigating the mechanisms underlying radiation therapy resistance in cancer. While some reports have suggested the involvement of circRNAs in modulating resistance to radiation therapy, the underpinning mechanisms remain unclear.

Methods

RT-qPCR and in situ hybridization were used to detect the expression level of circCDYL2 in nasopharyngeal carcinoma tissue samples. The effect of circCDYL2 on radiotherapy resistance in nasopharyngeal carcinoma was demonstrated by in vitro and in vivo functional experiments. The HR-GFP reporter assay determined that circCDYL2 affected homologous recombination repair. RNA pull down, RIP, western blotting, IF, and polysome profiling assays were used to verify that circCDYL2 promoted the translation of RAD51 by binding to EIF3D protein.

Results

We have identified circCDYL2 as highly expressed in nasopharyngeal carcinoma tissues, and it was closely associated with poor prognosis. In vitro and in vivo experiments demonstrate that circCDYL2 plays a pivotal role in promoting radiotherapy resistance in nasopharyngeal carcinoma. Our investigation unveils a specific mechanism by which circCDYL2, acting as a scaffold molecule, recruits eukaryotic translation initiation factor 3 subunit D protein (EIF3D) to the 5′-UTR of RAD51 mRNA, a crucial component of the DNA damage repair pathway to facilitate the initiation of RAD51 translation and enhance homologous recombination repair capability, and ultimately leads to radiotherapy resistance in nasopharyngeal carcinoma.

Conclusions

These findings establish a novel role of the circCDYL2/EIF3D/RAD51 axis in nasopharyngeal carcinoma radiotherapy resistance. Our work not only sheds light on the underlying molecular mechanism but also highlights the potential of circCDYL2 as a therapeutic sensitization target and a promising prognostic molecular marker for nasopharyngeal carcinoma.
Development and internal validation of an algorithm for estimating mortality in patients encountered by physician-staffed helicopter emergency medical services
Authors: Reitala Emil , Lääperi Mitja , Skrifvars Markus B. , Silfvast Tom , Vihonen Hanna , Toivonen Pamela , Tommila Miretta , Raatiniemi Lasse , Nurmi Jouni
Published: April 2024

Background

Severity of illness scoring systems are used in intensive care units to enable the calculation of adjusted outcomes for audit and benchmarking purposes. Similar tools are lacking for pre-hospital emergency medicine. Therefore, using a national helicopter emergency medical services database, we developed and internally validated a mortality prediction algorithm.

Methods

We conducted a multicentre retrospective observational register-based cohort study based on the patients treated by five physician-staffed Finnish helicopter emergency medical service units between 2012 and 2019. Only patients aged 16 and over treated by physician-staffed units were included. We analysed the relationship between 30-day mortality and physiological, patient-related and circumstantial variables. The data were imputed using multiple imputations employing chained equations. We used multivariate logistic regression to estimate the variable effects and performed derivation of multiple multivariable models with different combinations of variables. The models were combined into an algorithm to allow a risk estimation tool that accounts for missing variables. Internal validation was assessed by calculating the optimism of each performance estimate using the von Hippel method with four imputed sets.

Results

After exclusions, 30 186 patients were included in the analysis. 8611 (29%) patients died within the first 30 days after the incident. Eleven predictor variables (systolic blood pressure, heart rate, oxygen saturation, Glasgow Coma Scale, sex, age, emergency medical services vehicle type [helicopter vs ground unit], whether the mission was located in a medical facility or nursing home, cardiac rhythm [asystole, pulseless electrical activity, ventricular fibrillation, ventricular tachycardia vs others], time from emergency call to physician arrival and patient category) were included. Adjusted for optimism after internal validation, the algorithm had an area under the receiver operating characteristic curve of 0.921 (95% CI 0.918 to 0.924), Brier score of 0.097, calibration intercept of 0.000 (95% CI -0.040 to 0.040) and slope of 1.000 (95% CI 0.977 to 1.023).

Conclusions

Based on 11 demographic, mission-specific, and physiologic variables, we developed and internally validated a novel severity of illness algorithm for use with patients encountered by physician-staffed helicopter emergency medical services, which may help in future quality improvement.
Serum and cerebrospinal fluid neurofilament light chain and glial fibrillary acid protein levels in early and advanced stages of cerebral amyloid Angiopathy
Authors: Rasing Ingeborg , Voigt Sabine , Koemans Emma A. , de Kort Anna M. , van Harten Thijs W. , van Etten Ellis S. , van Zwet Erik W. , Stoops Erik , Francois Cindy , Kuiperij H. Bea , Klijn Catharina J.M. , Schreuder Floris H.B.M. , van der Weerd Louise , van Osch Matthias J.P. , van Walderveen Marianne A.A. , Verbeek Marcel M. , Terwindt Gisela M. , Wermer Marieke J.H.
Published: April 2024

Background

Neurofilament light chain (NFL) is a biomarker for neuroaxonal damage and glial fibrillary acidic protein (GFAP) for reactive astrocytosis. Both processes occur in cerebral amyloid angiopathy (CAA), but studies investigating the potential of NFL and GFAP as markers for CAA are lacking.

We aimed to investigate NFL and GFAP as biomarkers for neuroaxonal damage and astrocytosis in CAA.

Methods

For this cross-sectional study serum and cerebrospinal fluid (CSF) samples were collected between 2010 and 2020 from controls, (pre)symptomatic Dutch-type hereditary (D-CAA) mutation-carriers and participants with sporadic CAA (sCAA) from two prospective CAA studies at two University hospitals in the Netherlands. NFL and GFAP levels were measured with Simoa-assays. The association between NFL and GFAP levels and age, cognitive performance (MoCA), CAA-related MRI markers (CAA-CSVD-burden) and Aβ40 and Aβ42 levels in CSF were assessed with linear regression adjusted for confounders. The control group was divided in age < 55 and ≥55 years to match the specific groups.

Results

We included 187 participants: 28 presymptomatic D-CAA mutation-carriers (mean age 40 years), 29 symptomatic D-CAA participants (mean age 58 years), 59 sCAA participants (mean age 72 years), 33 controls < 55 years (mean age 42 years) and 38 controls ≥ 55 years (mean age 65 years).

In presymptomatic D-CAA, only GFAP in CSF (7.7*103pg/mL vs. 4.4*103pg/mL in controls; P<.001) was increased compared to controls. In symptomatic D-CAA, both serum (NFL:26.2pg/mL vs. 12.5pg/mL; P=0.008, GFAP:130.8pg/mL vs. 123.4pg/mL; P=0.027) and CSF (NFL:16.8*102pg/mL vs. 7.8*102pg/mL; P=0.01 and GFAP:11.4*103pg/mL vs. 7.5*103pg/mL; P<.001) levels were higher than in controls and serum levels (NFL:26.2pg/mL vs. 6.7pg/mL; P=0.05 and GFAP:130.8pg/mL vs. 66.0pg/mL; P=0.004) were higher than in pre-symptomatic D-CAA. In sCAA, only NFL levels were increased compared to controls in both serum (25.6pg/mL vs. 12.5pg/mL; P=0.005) and CSF (20.0*102pg/mL vs 7.8*102pg/mL; P=0.008). All levels correlated with age. Serum NFL correlated with MoCA (P=0.008) and CAA-CSVD score (P<.001). NFL and GFAP in CSF correlated with Aβ42 levels (P=0.01/0.02).

Conclusions

GFAP level in CSF is an early biomarker for CAA and is increased years before symptom onset. NFL and GFAP levels in serum and CSF are biomarkers for advanced CAA.
Comparing generative and extractive approaches to information extraction from abstracts describing randomized clinical trials
Authors: Witte Christian , Schmidt David M. , Cimiano Philipp
Published: April 2024

Background

Systematic reviews of Randomized Controlled Trials (RCTs) are an important part of the evidence-based medicine paradigm. However, the creation of such systematic reviews by clinical experts is costly as well as time-consuming, and results can get quickly outdated after publication. Most RCTs are structured based on the Patient, Intervention, Comparison, Outcomes (PICO) framework and there exist many approaches which aim to extract PICO elements automatically. The automatic extraction of PICO information from RCTs has the potential to significantly speed up the creation process of systematic reviews and this way also benefit the field of evidence-based medicine.

Results

Previous work has addressed the extraction of PICO elements as the task of identifying relevant text spans or sentences, but without populating a structured representation of a trial. In contrast, in this work, we treat PICO elements as structured templates with slots to do justice to the complex nature of the information they represent. We present two different approaches to extract this structured information from the abstracts of RCTs. The first approach is an extractive approach based on our previous work that is extended to capture full document representations as well as by a clustering step to infer the number of instances of each template type. The second approach is a generative approach based on a seq2seq model that encodes the abstract describing the RCT and uses a decoder to infer a structured representation of a trial including its arms, treatments, endpoints and outcomes. Both approaches are evaluated with different base models on a manually annotated dataset consisting of RCT abstracts on an existing dataset comprising 211 annotated clinical trial abstracts for Type 2 Diabetes and Glaucoma. For both diseases, the extractive approach (with ) reached the best $$F_1$$

F
1

score, i.e. 0.547 ($$\pm 0.006$$

±
0.006

) for type 2 diabetes and 0.636 ($$\pm 0.006$$

±
0.006

) for glaucoma. Generally, the $$F_1$$

F
1

scores were higher for glaucoma than for type 2 diabetes and the standard deviation was higher for the generative approach.

Conclusion

In our experiments, both approaches show promising performance extracting structured PICO information from RCTs, especially considering that most related work focuses on the far easier task of predicting less structured objects. In our experimental results, the extractive approach performs best in both cases, although the lead is greater for glaucoma than for type 2 diabetes. For future work, it remains to be investigated how the base model size affects the performance of both approaches in comparison. Although the extractive approach currently leaves more room for direct improvements, the generative approach might benefit from larger models.
Unveiling new horizons in heart research: the promise of multi-chamber cardiac organoids
Authors: Hou Junjie , Chen Ye-Guang , Xiong Jing-Wei
Published: April 2024

Human cardiac and other organoids have recently emerged as a groundbreaking tool for advancing our understanding the developmental biology of human organs. A recent paper from Sasha Mendjan’s laboratory published in the journal Cell on December 7, 2023, reported the generation of multi-chamber cardioids from human pluripotent stem cells, a transformative technology in the field of cardiology. In this short highlight paper, we summarize their findings. Their cardioids remarkably recapitulate the complexity of the human embryonic heart, including tissue architecture, cellular diversity, and functionality providing an excellent in vitro model for investigation of human heart development, disease modeling, precision medicine, and regenerative medicine. Thus, generating cardioids is an important step forward for understanding human heart development and developing potential therapies for heart diseases.
Blind Federated Learning without initial model
Authors: Salmeron Jose L. , Arévalo Irina
Published: April 2024

Federated learning is an emerging machine learning approach that allows the construction of a model between several participants who hold their own private data. This method is secure and privacy-preserving, suitable for training a machine learning model using sensitive data from different sources, such as hospitals. In this paper, the authors propose two innovative methodologies for Particle Swarm Optimisation-based federated learning of Fuzzy Cognitive Maps in a privacy-preserving way. In addition, one relevant contribution this research includes is the lack of an initial model in the federated learning process, making it effectively blind. This proposal is tested with several open datasets, improving both accuracy and precision.
Radiomics signature for dynamic changes of tumor-infiltrating CD8+ T cells and macrophages in cervical cancer during chemoradiotherapy
Authors: Huang Kang , Huang Xuehan , Zeng Chengbing , Wang Siyan , Zhan Yizhou , Cai Qingxin , Peng Guobo , Yang Zhining , Zhou Li , Chen Jianzhou , Chen Chuangzhen
Published: April 2024

Background

Our previous study suggests that tumor CD8+ T cells and macrophages (defined as CD68+ cells) infiltration underwent dynamic and heterogeneous changes during concurrent chemoradiotherapy (CCRT) in cervical cancer patients, which correlated with their short-term tumor response. This study aims to develop a CT image-based radiomics signature for such dynamic changes.

Methods

Thirty cervical squamous cell carcinoma patients, who were treated with CCRT followed by brachytherapy, were included in this study. Pre-therapeutic CT images were acquired. And tumor biopsies with immunohistochemistry at primary sites were performed at baseline (0 fraction (F)) and immediately after 10F. Radiomics features were extracted from the region of interest (ROI) of CT images using Matlab. The LASSO regression model with ten-fold cross-validation was utilized to select features and construct an immunomarker classifier and a radiomics signature. Their performance was evaluated by the area under the curve (AUC).

Results

The changes of tumor-infiltrating CD8+T cells and macrophages after 10F radiotherapy as compared to those at baseline were used to generate the immunomarker classifier (AUC= 0.842, 95% CI:0.680–1.000). Additionally, a radiomics signature was developed using 4 key radiomics features to predict the immunomarker classifier (AUC=0.875, 95% CI:0.753-0.997). The patients stratified based on this signature exhibited significant differences in treatment response (p = 0.004).

Conclusion

The radiomics signature could be used as a potential predictor for the CCRT-induced dynamic alterations of CD8+ T cells and macrophages, which may provide a less invasive approach to appraise tumor immune status during CCRT in cervical cancer compared to tissue biopsy.