bluuebunny/crossref_metadata_2025 huggingface dataset:
Circ_072697 knockdown promotes advanced glycation end products-induced cell proliferation and migration in HaCaT cells via miR-3150a-3p/KDM2A axis
Authors: Tian Ming , Tang Jiajun , Huang Rong , Dong Jiaoyun , Jia Huiying
Published: September 2023

Objective

Diabetes foot ulcer (DFU) is a serious complication of diabetes, which can lead to significant mortality and amputation rate. Our previous study found circ_072697 was highly expressed in DFU tissues, but the regulatory mechanism of circ_072697 in DFU remains unclear.

Methods

The relative expressions of circ_072697, miR-3150a-3p, and KDM2A in DFU patients or advanced glycation end products (AGEs)-treated HaCaT cells (used as DFU cell model) were determined by using qRT-PCR. Cell proliferation and migration abilities were determined by using CCK-8 and Transwell assays. The interaction between miR-3150a-3p with circ_072697 or KDM2A were verified by RNA immunoprecipitation (RIP) and dual-luciferase reporter assays. Furthermore, the protein expression of genes involved in MAPK signaling pathway was detected by western blot.

Results

The expression of circ_072697 was significantly upregulated in DFU tissues, while the expression of miR-3150a-3p was downregulated. Circ_072697 knockdown promoted the proliferation and migration of AGEs-treated HaCaT cells. miR-3150a-3p was confirmed as a target of circ_072697 and its inhibitor reversed the promotion effects of circ_072697 knockdown on biological behavior of cells. In addition, KDM2A was considered as a target of miR-3150a-3p and it was highly expressed in DFU samples. Importantly, circ_072697 could regulate KDM2A expression through sponging miR-3150a-3p, and this axis had effect on the MAPK signaling pathway.

Conclusions

Overall, circ_072697 regulated the biological behaviors of keratinocytes in DFU via miR-3150a-3p/KDM2A axis and MAPK signaling pathway, revealing a new insight into the pathogenesis and potential therapeutic targets of DFU.
Population attributable fractions of fatty liver disease for type 2 diabetes Mellitus
Authors: Xu Jingyuan , Wu Longyun , Deng Jiang , Yang Longbao , Wang Yatao , Tian Hongyang , Ji Yajun , Xia Qiaoyun , Han Zhiyi , Cheng Yan , Lu Xiaolan
Published: September 2023

Purpose

To determine the population attributable fraction (PAF) of fatty liver disease (FLD) for type 2 diabetes mellitus (T2DM) and compare it to the PAFs of other metabolic abnormalities.

Methods

We conducted a 10-year retrospective cohort study of 33,346 individuals in Karamay Central Hospital of Xinjiang. Individuals were followed up for T2DM occurrence based on FBS. The PAFs of FLD were calculated generally and respectively in different sex and age groups. A comparison of the PAF of FLD and that of other metabolic abnormalities, as well as the PAFs of FLD in different groups classified based on age and sex, was performed using Cox regression.

Results

During an average follow-up period of 3.71 years, 1486 T2DM were diagnosed. The incidence density of T2DM was 1.2/100 person-years, and cumulative incidence rate was 4456.31/100,000 person-years. Partial PAF (PAFp) of FLD in the entire population was 23.11%. In the male population, PAFp was higher at 30–40 years old. In the female population, it was higher when age ≥ 60 years old. In multivariable Cox regression model, FLD, male sex, age ≥ 45 years old, overweight, hypertriglyceridaemia, and systolic hypertension were independent risk factors for T2DM, with corresponding PAFp of 25.00%, 24.99%, 36.47%, 24.96%, 5.71%, and 6.76%, respectively. Age ≥ 45 years old showed the highest PAFp and adjusted hazard ratio, followed by FLD.

Conclusions

FLD contributes more to T2DM incidence than other metabolic disorders. Particular attention should be given to male populations of 30–40 and female populations above 60 for FLD prevention and treatment.
Incidence, clinical characteristics, and survival outcomes of ovarian strumal diseases: a retrospective cohort study
Authors: Li Sijian , Hong Ruping , Yin Min , Zhang Tianyu , Zhang Xinyue , Yang Jiaxin
Published: September 2023

Background

Struma ovarii (SO) is a rare tumor and may transform into ovarian strumal carcinoid (OSC) and/or malignant struma ovarii (MSO), but the incidence, clinical characteristics, and survival outcomes have not been well defined.

Methods

We conducted a retrospective study of patients with ovarian strumal diseases treated in the our hospital between 1980 and 2022. Subgroup analyses of SO, OSC, and MSO were subsequently performed.

Results

A total of 275 cases (2.14%) were identified in a cohort of 12,864 patients with ovarian teratomas, where SO, OSC, and MSO accounted for 83.3%, 12.0%, and 4.7% of cases, respectively. There were no significant differences in age, tumor sizes, elevated tumor markers, and ascites among the three subgroups. At initial treatment, all patients with SO or OSC had FIGO stage I disease except one SO patient presenting metastatic disease, ten patients had MSO confined to the ovary, whereas other three patients had metastatic diseases. Two patients with SO respectively relapsed at peritoneum and anterior mesorectum, while none of the OSC patients presented tumor recurrence or death despite different surgical procedures employed. The 5-year recurrence-free survival rate was 88.9%, and only one death occurred at 9.5 years after diagnosis in patients with MSO. Radioiodine therapy showed satisfactory therapeutic efficacy, but these patients showed poor responses to the chemotherapy.

Conclusion

2.14% of ovarian teratoma could be classified as SO, of which 12.0% and 4.7% of SO may transform into OSC and MSO, repsectively. The survival outcomes were excellent even after SO transformed into OSC or MSO.

Synopsis

SO occupied 2.14% of ovarian teratoma, where 12.0% and 4.7% of SO may transform into OSC and MSO, respectively, and had excellent survival outcomes.
Transvaginal small bowel evisceration after cervical loop electrosurgical excision procedure: a case report
Authors: Yao Kui , Xie Chuan
Published: September 2023

Transvaginal small bowel evisceration is a life-threatening condition, which is usually seen in postmenopausal women with a history of gynecological surgery. Cervical loop electrosurgical excision procedure (LEEP) is widely used in the treatment of cervical intraepithelial neoplasia (CIN), and its surgical risk and postoperative complications are relatively low because of the simplicity of the operation. However, improper operation may result in perforation of the uterus, which can cause prolapse of the small bowel into the vagina. We here reported an extremely rare case of a young woman with transvaginal small bowel evisceration after cervical LEEP, achieving a good prognosis after the prolapsed bowel was reduced. The patient underwent cervical LEEP as a treatment for CIN III, but the LEEP resulted in a laceration of about 4.0 cm × 3.5 cm on the peritoneum of the uterovesical peritoneal reflection and a laceration of about 2.0 cm × 1.5 cm on the anterior wall of the cervical canal. Through the two lacerations, the pelvic cavity is connected to the vagina and the small intestine prolapsed into the vagina. Due to aggressive surgical intervention, the patient achieved a favorable prognosis after successfully reducing the prolapsed bowel.
Expanding the non-technical skills vocabulary of operating room nurses: a qualitative study
Authors: Sirevåg Irene , Tjoflåt Ingrid , Hansen Britt Sætre
Published: September 2023

Background

Operating room nurses have specialised technical and non-technical skills and are essential members of the surgical team. The profession’s dependency of tacit knowledge has made their non-technical skills difficult to access for researchers, thus, creating limitations in the identification of the non-technical skills of operating room nurses. Non-technical skills are categorised in the crew resource management framework, and previously, non-technical skills of operating room nurses have been identified within the scope of the framework. The purpose of this study is to explore operating room nurses’ descriptions of their practices in search for non-technical skills not included in the crew resource management framework.

Methods

This study has a qualitative design. An expert panel of experienced operating room nurses (N = 96) in Norway provided qualitative descriptions of their practice in a Delphi survey. The data were analysed in an inductive thematic analysis. This study was conducted and reported in line with Standards for Reporting Qualitative Research (SRQR).

Results

The inductive thematic analysis developed two themes, ‘Ethical competence’ and ‘Professional accountability’, that encompass operating room nurses’ novel descriptions of their non-technical skills. The participants take pride in having the patients’ best interest as their main objective even if this may threaten their position in the team.

Conclusions

This study has identified novel non-technical skills that are not described in the crew resource management framework. These findings will contribute to the development of a new behavioural marker system for the non-technical skills of operating room nurses. This system will facilitate verbalisation of tacit knowledge and contribute to an increased knowledge about the operating room nursing profession.
macJNet: weakly-supervised multimodal image deformable registration using joint learning framework and multi-sampling cascaded MIND
Authors: Zhou Zhiyong , Hong Ben , Qian Xusheng , Hu Jisu , Shen Minglei , Ji Jiansong , Dai Yakang
Published: September 2023

Deformable multimodal image registration plays a key role in medical image analysis. It remains a challenge to find accurate dense correspondences between multimodal images due to the significant intensity distortion and the large deformation. macJNet is proposed to align the multimodal medical images, which is a weakly-supervised multimodal image deformable registration method using a joint learning framework and multi-sampling cascaded modality independent neighborhood descriptor (macMIND). The joint learning framework consists of a multimodal image registration network and two segmentation networks. The proposed macMIND is a modality-independent image structure descriptor to provide dense correspondence for registration, which incorporates multi-orientation and multi-scale sampling patterns to build self-similarity context. It greatly enhances the representation ability of cross-modal features in the registration network. The semi-supervised segmentation networks generate anatomical labels to provide semantics correspondence for registration, and the registration network helps to improve the performance of multimodal image segmentation by providing the consistency of anatomical labels. 3D CT-MR liver image dataset with 118 samples is built for evaluation, and comprehensive experiments have been conducted to demonstrate that macJNet achieves superior performance over state-of-the-art multi-modality medical image registration methods.
Improving milk donation behavior through an educational intervention based on the theory of planned behavior: study protocol of a cluster randomized controlled trial
Authors: Shahbazi Sighaldeh Shirin , Moridi Maryam , Ghorban Sabagh Vafa , Kazemnejad Anoshirvan , Shateranni Fatemeh
Published: September 2023

Background

Breastfeeding mothers’ decisions to donate their milk is influenced by their knowledge, attitudes, and subjective norms such as their family’s opinions on milk donation. In Iran, women have favorable knowledge and positive attitudes toward breastfeeding, but they lack sufficient information and education about milk banks. With respect to current childbearing policies, an increase in the number of infants who will be admitted to neonatal intensive care units is expected. Accordingly, improving milk donation behavior, which requires mothers’ intention and ability to donate breast milk, is important for infants’ survival and well-being. Therefore, this study aims to evaluate whether an educational program based on the theory of planned behavior affects breastfeeding mothers’ decisions to donate their breast milk.

Methods

This cluster randomized controlled trial will be conducted in health centers affiliated to Tehran University of Medical Sciences and will enroll 66 breastfeeding mothers (intervention, n = 33; control, n = 33). After collecting baseline data, the intervention group will begin receiving a 60-minute weekly educational program based on Theory of Planned Behavior components for four weeks. The first follow-up assessment will be conducted immediately after the intervention, and the final one will be conducted 12 weeks later. The primary outcomes are the number of mothers who have donated their breast milk and changes in breastfeeding mothers’ knowledge, attitude, subjective norms, and perceived behavioral control about donor human milk and intention to donate milk.

Discussion

This trial will evaluate if a well-designed educational program can improve breastfeeding mothers’ knowledge and promote their behavioral factors regarding milk donation and lead to a significant increase in the number of potential milk donors.

Trial registration

irct.ir (IRCT20230124057203N1) registered February 14, 2023.
ScRNA analysis and ferroptosis-related ceRNA regulatory network investigation in microglia cells at different time points after spinal cord injury
Authors: Bao Junping , Yang Shu
Published: September 2023

Spinal cord injuries (SCI) are usually caused by mechanical trauma that leads to serious physical and psychological damage to the patient as well as a huge economic burden to the whole society. The prevention, treatment, and rehabilitation of spinal cord injuries have become a major issue for the medical community today due to the enormous social and economic expenditure induced via spinal cord injuries. Therefore, in-depth research into SCI is necessary. Microglia have been shown to be the key player in the immune inflammatory response after spinal cord injury, but the mechanisms of immune regulation at different time points after spinal cord injury remain unclear. To investigate the inflammatory biomarkers associated with microglia at different time points after SCI, we downloaded single-cell RNA sequencing data from mouse spinal cords 3- and 14-days after the injury and identified subpopulations associated with microglia. Further functional enrichment analysis also confirmed that microglia are associated with immune system regulation at different time points and that both can modulate cytokine production. As ferroptosis is a newly identified non-apoptotic programmed cell death, microglia establish a bridge between ferroptosis and CNS inflammation and may play an important role in spinal cord injury. We then screened for genes differentially expressed in microglia during 3- and 14-days after spinal cord injury and associated with iron death, named Stmn1 and Fgfbr1, respectively, and verified that these pivotal genes are closely related to the immune cells. Finally, we also screened for drug fractions associated with these pivotal genes. Our results predict key genes in the immune inflammatory process associated with microglia at different time points after spinal cord injury at the single-cell level and provide a molecular basis for better treatment of SCI.
CircRNF10 triggers a positive feedback loop to facilitate progression of glioblastoma via redeploying the ferroptosis defense in GSCs
Authors: Wang Chengbin , Zhang Minjie , Liu Yingliang , Cui Daming , Gao Liang , Jiang Yang
Published: September 2023

Background

Glioma exhibit heterogeneous susceptibility for targeted ferroptosis. How circRNAs alterations in glioma promote iron metabolism and ferroptosis defense remains unclarified.

Methods

The highly enriched circRNAs in glioblastoma (GBM) were obtained through analysis of sequencing datasets. Quantitative real-time PCR (qRT–PCR) was used to determine the expression of circRNF10 in glioma and normal brain tissue. Both gain-of-function and loss-of-function studies were used to assess the effects of circRNF10 on ferroptosis using in vitro and in vivo assays. The hypothesis that ZBTB48 promotes ferroptosis defense was established using bioinformatics analysis and functional assays. RNA pull-down and RNA immunoprecipitation (RIP) assays were performed to examine the interaction between circRNF10 and target proteins including ZBTB48, MKRN3 and IGF2BP3. The posttranslational modification mechanism of ZBTB48 was verified using coimmunoprecipitation (co-IP) and ubiquitination assays. The transcription activation of HSPB1 and IGF2BP3 by ZBTB48 was confirmed through luciferase reporter gene and chromatin immunoprecipitation (ChIP) assays. The stabilizing effect of IGF2BP3 on circRNF10 was explored by actinomycin D assay. Finally, a series of in vivo experiments were performed to explore the influences of circRNF10 on the glioma progression.

Results

A novel circular RNA, hsa_circ_0028912 (named circRNF10), which is significantly upregulated in glioblastoma tissues and correlated with patients’ poor prognosis. Through integrated analysis of the circRNA-proteins interaction datasets and sequencing results, we reveal ZBTB48 as a transcriptional factor binding with circRNF10, notably promoting upregulation of HSPB1 and IGF2BP3 expression to remodel iron metabolism and facilitates the launch of a circRNF10/ZBTB48/IGF2BP3 positive feedback loop in GSCs. Additionally, circRNF10 can competitively bind to MKRN3 and block E3 ubiquitin ligase activity to enhance ZBTB48 expression. Consequently, circRNF10-overexpressed glioma stem cells (GSCs) display lower Fe2+ accumulation, selectively priming tumors for ferroptosis evading.

Conclusion

Our research presents abnormal circRNAs expression causing a molecular and metabolic change of glioma, which we leverage to discover a therapeutically exploitable vulnerability to target ferroptosis.
Report and follow-up on two new patients with congenital mesoblastic nephroma
Authors: Serra Gregorio , Cimador Marcello , Giuffrè Mario , Insinga Vincenzo , Montante Claudio , Pensabene Marco , Piro Ettore , Salerno Sergio , Schierz Ingrid Anne Mandy , Corsello Giovanni
Published: September 2023

Background

Tumors are rare in neonatal age. Congenital mesoblastic nephroma (CMN) is a usually benign renal tumor observed at birth, or in the first months of life. It may also be identified prenatally and associated with polyhydramnios leading to preterm delivery. Effective treatment is surgical in most cases, consisting in total nephrectomy. In literature, very few studies report on the neonatal management of such a rare disease, and even less are those describing its uncommon complications.

Cases presentation

We report on two single-center newborns affected with CMN. The first patient is a preterm female baby, born at 30+ 1 weeks of gestation (WG) due to premature labor, with prenatal (25 WG) identification of an intra-abdominal fetal mass associated with polyhydramnios. Once obtained the clinical stability, weight gain, instrumental (computed tomography, CT, showing a 4.8 × 3.3 cm left renal neoformation) and histological/molecular characterization of the lesion (renal needle biopsy picture of classic CMN with ETV6-NTRK3 translocation), a left nephrectomy was performed at 5 weeks of chronological age. The following clinical course was complicated by intestinal obstruction due to bowel adherences formation, then by an enterocutaneous fistula, requiring multiple surgical approaches including transitory ileo- and colostomy, before the conclusive anastomoses intervention. The second patient is a 17-day-old male term baby, coming to our observation due to postnatal evidence of palpable left abdominal mass (soon defined through CT, showing a 7.5 × 6.5 cm neoformation in the left renal lodge), feeding difficulties and poor weight gain. An intravenous diuretic treatment was needed due to the developed hypertension and hypercalcemia, which regressed after the nephrectomy (histological diagnosis of cellular CMN with ETV6-NTRK3 fusion) performed at day 26. In neither case was chemotherapy added. Both patients have been included in multidisciplinary follow-up, they presently show regular growth and neuromotor development, normal renal function and no local/systemic recurrences or other gastrointestinal/urinary disorders.

Conclusions

The finding of a fetal abdominal mass should prompt suspicion of CMN, especially if it is associated with polyhydramnios; it should also alert obstetricians and neonatologists to the risk of preterm delivery. Although being a usually benign condition, CMN may be associated with neonatal systemic-metabolic or postoperative complications. High-level surgical expertise, careful neonatological intensive care and histopathological/cytogenetic-molecular definition are the cornerstones for the optimal management of patients. This should also include an individualized follow-up, oriented to the early detection of any possible recurrences or associated anomalies and to a better quality of life of children and their families.
Inferring chromatin accessibility during murine hematopoiesis through phylogenetic analysis
Authors: Koyanagi Kanako O.
Published: September 2023

Objective

Diversification of cell types and changes in epigenetic states during cell differentiation processes are important for understanding development. Recently, phylogenetic analysis using DNA methylation and histone modification information has been shown useful for inferring these processes. The purpose of this study was to examine whether chromatin accessibility data can help infer these processes in murine hematopoiesis.

Results

Chromatin accessibility data could partially infer the hematopoietic differentiation hierarchy. Furthermore, based on the ancestral state estimation of internal nodes, the open/closed chromatin states of differentiating progenitor cells could be predicted with a specificity of 0.86–0.99 and sensitivity of 0.29–0.72. These results suggest that the phylogenetic analysis of chromatin accessibility could offer important information on cell differentiation, particularly for organisms from which progenitor cells are difficult to obtain.
Dual-layer spectral-detector CT for predicting microsatellite instability status and prognosis in locally advanced gastric cancer
Authors: Zhu Yongjian , Wang Peng , Wang Bingzhi , Jiang Zhichao , Li Ying , Jiang Jun , Zhong Yuxin , Xue Liyan , Jiang Liming
Published: September 2023

Objective

To construct and validate a prediction model based on dual-layer detector spectral CT (DLCT) and clinico-radiologic features to predict the microsatellite instability (MSI) status of gastric cancer (GC) and to explore the relationship between the prediction results and patient prognosis.

Methods

A total of 264 GC patients who underwent preoperative DLCT examination were randomly allocated into the training set (n = 187) and validation set (n = 80). Clinico-radiologic features and DLCT parameters were used to build the clinical and DLCT model through multivariate logistic regression analysis. A combined DLCT parameter (CDLCT) was constructed to predict MSI. A combined prediction model was constructed using multivariate logistic regression analysis by integrating the significant clinico-radiologic features and CDLCT. The Kaplan–Meier survival analysis was used to explore the prognostic significant of the prediction results of the combined model.

Results

In this study, there were 70 (26.52%) MSI-high (MSI-H) GC patients. Tumor location and CT_N staging were independent risk factors for MSI-H. In the validation set, the area under the curve (AUC) of the clinical model and DLCT model for predicting MSI status was 0.721 and 0.837, respectively. The combined model achieved a high prediction efficacy in the validation set, with AUC, sensitivity, and specificity of 0.879, 78.95%, and 75.4%, respectively. Survival analysis demonstrated that the combined model could stratify GC patients according to recurrence-free survival (p = 0.010).

Conclusion

The combined model provides an efficient tool for predicting the MSI status of GC noninvasively and tumor recurrence risk stratification after surgery.

Critical relevance statement

MSI is an important molecular subtype in gastric cancer (GC). But MSI can only be evaluated using biopsy or postoperative tumor tissues. Our study developed a combined model based on DLCT which could effectively predict MSI preoperatively. Our result also showed that the combined model could stratify patients according to recurrence-free survival. It may be valuable for clinicians in choosing appropriate treatment strategies to avoid tumor recurrence and predicting clinical prognosis in GC.

Key points

• Tumor location and CT_N staging were independent predictors for MSI-H in GC.

• Quantitative DLCT parameters showed potential in predicting MSI status in GC.

• The combined model integrating clinico-radiologic features and CDLCT could improve the predictive performance.

• The prediction results could stratify the risk of tumor recurrence after surgery.

Graphical Abstract
Cell-free therapy based on extracellular vesicles: a promising therapeutic strategy for peripheral nerve injury
Authors: Namini Mojdeh Salehi , Daneshimehr Fatemeh , Beheshtizadeh Nima , Mansouri Vahid , Ai Jafar , Jahromi Hossein Kargar , Ebrahimi-Barough Somayeh
Published: September 2023

Peripheral nerve injury (PNI) is one of the public health concerns that can result in a loss of sensory or motor function in the areas in which injured and non-injured nerves come together. Up until now, there has been no optimized therapy for complete nerve regeneration after PNI. Exosome-based therapies are an emerging and effective therapeutic strategy for promoting nerve regeneration and functional recovery. Exosomes, as natural extracellular vesicles, contain bioactive molecules for intracellular communications and nervous tissue function, which could overcome the challenges of cell-based therapies. Furthermore, the bioactivity and ability of exosomes to deliver various types of agents, such as proteins and microRNA, have made exosomes a potential approach for neurotherapeutics. However, the type of cell origin, dosage, and targeted delivery of exosomes still pose challenges for the clinical translation of exosome therapeutics. In this review, we have focused on Schwann cell and mesenchymal stem cell (MSC)-derived exosomes in nerve tissue regeneration. Also, we expressed the current understanding of MSC-derived exosomes related to nerve regeneration and provided insights for developing a cell-free MSC therapeutic strategy for nerve injury.
Expansion of human bone marrow-derived mesenchymal stromal cells with enhanced immunomodulatory properties
Authors: Neo Shu Hui , Her Zhisheng , Othman Rashidah , Tee Ching Ann , Ong Li Ching , Wang Yuehua , Tan Irwin , Tan Jaylen , Yang Yanmeng , Yang Zheng , Chen Qingfeng , Boyer Laurie A.
Published: September 2023

Background

Mesenchymal stromal cells (MSCs) have broad potential as a cell therapy including for the treatment of drug-resistant inflammatory conditions with abnormal T cell proliferation such as graft-versus-host disease (GVHD). Clinical success, however, has been complicated by the heterogeneity of culture-expanded MSCs as well as donor variability. Here, we devise culture conditions that promote expansion of MSCs with enhanced immunomodulatory functions both in vitro and in animal models of GVHD.

Methods

Human bone marrow-derived MSCs were expanded at high-confluency (MSCHC) and low-confluency state (MSCLC). Their immunomodulatory properties were evaluated with in vitro co-culture assays based on suppression of activated T cell proliferation and secretion of pro-inflammatory cytokines from activated T cells. Metabolic state of these cells was determined, while RNA sequencing was performed to explore transcriptome of these MSCs. Ex vivo expanded MSCHC or MSCLC was injected into human peripheral blood mononuclear cells (PBMC)-induced GVHD mouse model to determine their in vivo therapeutic efficacy based on clinical grade scoring, human CD45+ blood count and histopathological examination.

Results

As compared to MSCLC, MSCHC significantly reduced both the proliferation of anti-CD3/CD28-activated T cells and secretion of pro-inflammatory cytokines upon MSCHC co-culture across several donors even in the absence of cytokine priming. Mechanistically, metabolic analysis of MSCHC prior to co-culture with activated T cells showed increased glycolytic metabolism and lactate secretion compared to MSCLC, consistent with their ability to inhibit T cell proliferation. Transcriptome analysis further revealed differential expression of immunomodulatory genes including TRIM29, BPIFB4, MMP3 and SPP1 in MSCHC as well as enriched pathways including cytokine–cytokine receptor interactions, cell adhesion and PI3K-AKT signalling. Lastly, we demonstrate in a human PBMC-induced GVHD mouse model that delivery of MSCHC showed greater suppression of inflammation and improved outcomes compared to MSCLC and saline controls.

Conclusion

Our study provides evidence that ex vivo expansion of MSCs at high confluency alters the metabolic and transcriptomic states of these cells. Importantly, this approach maximizes the production of MSCs with enhanced immunomodulatory functions without priming, thus providing a non-invasive and generalizable strategy for improving the use of MSCs for the treatment of inflammatory diseases.
Exploring the ability of machine learning-based virtual screening models to identify the functional groups responsible for binding
Authors: Hadfield Thomas E. , Scantlebury Jack , Deane Charlotte M.
Published: September 2023

Many recently proposed structure-based virtual screening models appear to be able to accurately distinguish high affinity binders from non-binders. However, several recent studies have shown that they often do so by exploiting ligand-specific biases in the dataset, rather than identifying favourable intermolecular interactions in the input protein-ligand complex. In this work we propose a novel approach for assessing the extent to which machine learning-based virtual screening models are able to identify the functional groups responsible for binding. To sidestep the difficulty in establishing the ground truth importance of each atom of a large scale set of protein-ligand complexes, we propose a protocol for generating synthetic data. Each ligand in the dataset is surrounded by a randomly sampled point cloud of pharmacophores, and the label assigned to the synthetic protein-ligand complex is determined by a 3-dimensional deterministic binding rule. This allows us to precisely quantify the ground truth importance of each atom and compare it to the model generated attributions. Using our generated datasets, we demonstrate that a recently proposed deep learning-based virtual screening model, PointVS, identified the most important functional groups with 39% more efficiency than a fingerprint-based random forest, suggesting that it would generalise more effectively to new examples. In addition, we found that ligand-specific biases, such as those present in widely used virtual screening datasets, substantially impaired the ability of all ML models to identify the most important functional groups. We have made our synthetic data generation framework available to facilitate the benchmarking of new virtual screening models. Code is available at https://github.com/tomhadfield95/synthVS.
A novel model for representing a plane target and finding the worst-case coverage in wireless sensor network based on Clifford algebra
Authors: Mahfouz Amr M. , Ismail Ahmed S. , El Sobky Wageda I. , Nasry Hany
Published: September 2023

Wireless ad hoc sensor networks have recently emerged as a premier research topic. They have great long-term economic potential and ability to transform our lives and pose many new system building challenges. Sensor networks also pose a number of new conceptual and optimization problems. Most of researches in wireless sensor networks are focused in obtaining better target coverage in order to reduce energy and cost of the network. The problem of planar target analysis is one of the crucial problems that should be considered while studying coverage problem of sensor networks. By combining computational geometry and graph theoretic techniques, specifically the Voronoi diagram and graph search algorithms, this paper introduces a novel sensor network coverage model that deals with plane target problem based on Clifford algebra which is a powerful tool that is coordinate free. Also, the calculations of the node coverage rate for the plane target in the sensor network using Clifford algebra are presented. Then, the maximum clearance path (worst-case coverage) of the sensor network for a plane target is proposed. The optimality and reliability of the proposed algorithm have been proved using simulation. Also, a comparison between the breach weight of the point target and the plane target is provided.
Mapping of nutrition policies and programs in South Asia towards achieving the Global Nutrition targets
Authors: Wali Nidhi , Agho Kingsley Emwinyore , Renzaho Andre M. N.
Published: September 2023

Background

South Asia continues to host the triple burden of child malnutrition with high levels of child undernutrition, hidden hunger (micronutrient deficiencies) and childhood overweight/obesity. To combat malnutrition, the international community along with the National governments have launched initiatives to track the country’s progress towards achieving the Global Nutrition targets by 2025. This review captures the country-specific efforts of nutrition-specific and nutrition-sensitive sectoral programs and policies towards achieving these targets for eight South Asian countries.

Methods

A systematic internet search was undertaken to search relevant policies and programs from Government websites and twelve International Organisations working in the region. The authors developed a template to map the policies against the following criteria: (i) enabling supportive environment; (ii) Initiatives targeted at nutrition-specific interventions; and (iii) Initiatives targeted at nutrition-specific interventions that impact child malnutrition. A narrative descriptive approach was used to present findings.

Results

All eight countries had relevant policies and programs to address child malnutrition and macronutrient deficiencies with targets for significant reductions in stunting and improved breastfeeding. However, despite the outlined there are major challenges of implementation, monitoring, evaluation and quality that persist with increased dependency on international donors and organisations for funding and/or implementation of nutrition plans.

Conclusion

There is a need to contextualise efforts designated to donors and governments to improve the tracking of efforts that impact nutrition.
The entrepreneurial ecosystem and the performance of micro and small enterprises (MSEs) in Amhara region, Ethiopia: the political–legal perspective
Authors: Wube Mulugeta Chane , Atwal Heena
Published: September 2023

All other parts of the entrepreneurial ecosystem in any country are commonly governed by the political and legal aspects of the entrepreneurial ecosystem. This is a novel approach that examines the integrated effect of the entrepreneurial ecosystem's political–legal subsystem on the performance of MSEs based on system theory and the mediating role of entrepreneurial competence taking a resource-based view in to account. There has been no detailed examination of the entrepreneurial ecosystem of MSEs in Africa in general, and Ethiopia in particular. A total sample of 499 MSE operators engaged in the three priority sectors: manufacturing, construction and urban agriculture was selected from the population of 4086 operators in three metropolitan cities of Amhara National Regional State, Ethiopia, using a proportional stratified sampling. Though the political–legal aspects of the entrepreneurial ecosystem have a major impact on both entrepreneurial competency and MSE’s performance, the relationship between entrepreneurial competencies and MSE performance was found to be insignificant. The role of entrepreneurial competency in mediating the relationships between policy and business performance and other business environments and business performance was shown to be insignificant. It is suggested by the study that the policies that the government designs concerning MSEs should be workable and attractive including the provision of different incentives. Lastly, other researchers in the area are suggested to further clarify the contradictions in the findings regarding the relationship between entrepreneurial competencies and the performance of SMEs.
Association between the Triglyceride–Glucose Index and Non-Alcoholic Fatty Liver Disease in patients with Atrial Fibrillation
Authors: Li Xiaozhong , Zhan Fenfang , Peng Tian , Xia Zhen , Li Juxiang
Published: September 2023

Background

The triglyceride and glucose index (TyG), as a surrogate of insulin resistance (IR), is closely associated with non-alcoholic fatty liver disease (NAFLD). However, the association between the TyG index and NAFLD in atrial fibrillation (AF) is unknown. Therefore, the purpose of this study is to explore the association between the TyG index and NAFLD in AF.

Methods

This retrospective study was performed at Nanchang University’s Second Affiliated Hospital. The AF patients who were hospitalized from January 2021 to December 2022 were enrolled. The association between the TyG index and NAFLD in AF patients was assessed by logistic regression and restricted cubic spline analysis. The ability of TyG index for identifying NAFLD was estimated by the area under the receiver operating characteristic (ROC).

Results

In this study, 632 people participated in the final analysis, with 176 (27.84%) having NAFLD. In the full adjustment model, there is an association between the TyG index and NAFLD [per 1 unit increment; odds ratios (ORs): 3.28; 95% confidence interval (CI) 2.14, 5.03]. Compared to the lowest tertile (TyG index < 8.29), the ORs for the highest tertile (TyG index ≥ 8.82) were 4.15 (95%CI: 2.28, 7.53). Dose–response analysis showed that the TyG index and NAFLD have a nearly linear relationship (P non-linear = 0.71). The area under the curve (AUC) of the TyG index is 0.735.

Conclusions

Our findings showed a significant association between the TyG index and NAFLD. The TyG index may be a good marker for predicting NAFLD in AF patients.
KL is a favorable prognostic factor related immune for clear cell renal cell carcinoma
Authors: Pan Ke-Hao , Yao Liqing , Chen Zhihao , Sun Jiale , Jia Zongming , Zhang Jianglei , Ling Zhixin
Published: September 2023

Background

Clear cell renal cell carcinoma (ccRCC) is a prevalent cancer in adult urology, often leading to metastasis and poor prognosis. Recently, advances in tumor immunology and aging research have opened up new possibilities for the treatment of kidney cancer. Therefore, the identification of potential targets and prognostic biomarkers for immunotherapy has become increasingly urgent.

Methods

Using GSE168845 data, we identified immune-aging-associated differentially expressed genes (IAR-DEGs) by intersecting differentially expressed immune-related genes and aging-related genes. The prognostic value of IAR-DEGs was determined via univariate and multivariate Cox regression analysis, revealing KL as an independent prognostic factor for ccRCC. We also investigated the correlation between KL and various immune-related factors, including immune cell infiltration, immune score, immune checkpoint, MSI, and TIED score. To confirm the expression of KL in ccRCC, we conducted qRT-PCR assays on both ccRCC cell lines and clinical tissue samples, and compared KL expression levels between normal kidney cell line (HK-2) and ACHN, a ccRCC cell line. Finally, we assessed KL protein expression levels in tissues using immunohistochemistry (IHC).

Results

In this study, we utilized Venn diagram analysis to identify 17 co-expressed immune-aging related DEGs from GSE168845, import database, and MSigDB database. GO and KEGG analysis revealed that the functions of the 17 IAR-DEGs were primarily related to “aging”. Univariate and multivariate Cox analysis validated these 17 genes, and KL was determined to be an independent prognostic factor for ccRCC. The downregulation of KL was observed in ccRCC tissues and was negatively associated with T stage, M stage, pathological stage, and histologic grade (p < 0.05). This downregulation indicated disease deterioration and a shortened overall survival period. Our calibration curves and nomogram demonstrated the excellent predictive potential of KL. GSEA analysis showed that KL gene mediated immune and aging-related pathways, and was significantly correlated with immune infiltration and MS and TIED score. More research has revealed a significant reduction in KL mRNA expression levels in human renal cancer cells, particularly in ccRCC tissues compared to adjacent normal kidney tissues. Moreover, immunohistochemistry data have demonstrated a marked decrease in KL protein expression levels in ccRCC cells when compared to adjacent normal tissues.

Conclusions

KL was a potential aging-related target for immunotherapy and valid prognostic biomarker for ccRCC patients.
Effect of JAK inhibitors on the three forms of bone damage in autoimmune arthritis: joint erosion, periarticular osteopenia, and systemic bone loss
Authors: Komagamine Masatsugu , Komatsu Noriko , Ling Rui , Okamoto Kazuo , Tianshu Shi , Matsuda Kotaro , Takeuchi Tsutomu , Kaneko Yuko , Takayanagi Hiroshi
Published: September 2023

Background

The types of bone damage in rheumatoid arthritis (RA) include joint erosion, periarticular osteoporosis, and systemic osteoporosis. Janus kinase (JAK) inhibitors ameliorate inflammation and joint erosion in RA, but their effect on the three types of bone loss have not been reportedly explored in depth. We aimed to clarify how JAK inhibitors influence the various types of bone loss in arthritis by modulating osteoclastic bone resorption and/or osteoblastic bone formation.

Methods

Collagen-induced arthritis (CIA) mice were treated with a JAK inhibitor after the onset of arthritis. Micro-computed tomography (μCT) and histological analyses (bone morphometric analyses) on the erosive calcaneocuboid joint, periarticular bone (distal femur or proximal tibia), and vertebrae were performed. The effect of four different JAK inhibitors on osteoclastogenesis under various conditions was examined in vitro.

Results

The JAK inhibitor ameliorated joint erosion, periarticular osteopenia and systemic bone loss. It reduced the osteoclast number in all the three types of bone damage. The JAK inhibitor enhanced osteoblastic bone formation in the calcaneus distal to inflammatory synovium in the calcaneocuboid joints, periarticular region of the tibia and vertebrae, but not the inflamed calcaneocuboid joint. All the JAK inhibitors suppressed osteoclastogenesis in vitro to a similar extent in the presence of osteoblastic cells. Most of the JAK inhibitors abrogated the suppressive effect of Th1 cells on osteoclastogenesis by inhibiting IFN-γ signaling in osteoclast precursor cells, while a JAK inhibitor did not affect this effect due to less ability to inhibit IFN-γ signaling.

Conclusions

The JAK inhibitor suppressed joint erosion mainly by inhibiting osteoclastogenesis, while it ameliorated periarticular osteopenia and systemic bone loss by both inhibiting osteoclastogenesis and promoting osteoblastogenesis. These results indicate that the effect of JAK inhibitors on osteoclastogenesis and osteoblastogenesis depends on the bone damage type and the affected bone area. In vitro studies suggest that while JAK inhibitors inhibit osteoclastic bone resorption, their effects on osteoclastogenesis in inflammatory environments vary depending on the cytokine milieu, JAK selectivity and cytokine signaling specificity. The findings reported here should contribute to the strategic use of antirheumatic drugs against structural damages in RA.
Nailfold capillaroscopy in Egyptian systemic lupus erythematosus (SLE) patients: correlation with demographic features and serum levels of IL 17A and IFNs I
Authors: Nasser Mohamed , Wadie Mary , Farid Alyaa , Amir Azza El
Published: September 2023

Background

In SLE patients, cytokines are linked to endothelial cell damage. Nailfold capillaroscopy (NFC) is a simple method for evaluating micro-vascular abnormalities in different connective tissue diseases (CTDs). The study aimed to detect the levels of interleukin 17A (IL 17A), type I interferons (IFNs I) in the serum, and NFC changes in Egyptian SLE patients compared to a control group and to correlate NFC findings with patients’ demographic features and serum levels of IL 17A and IFNs I.

Results

Serum levels of IL 17A, IFN α, and IFN β were significantly higher in SLE patients than in control group (P < 0.0001). About thirty nine patients (73.6%) of the 53 SLE patients showed abnormal NFC changes. Egyptian SLE patients had a high prevalence of the NFC non-specific pattern, with 32 (60.4%) patients showing non-specific changes and 7 (13.2%) patients showing scleroderma pattern, including 3 (5.6%) patients with active scleroderma pattern and 4 (7.55%) patients with late scleroderma pattern. Furthermore, Raynaud’s phenomenon (RP) was observed in 8 (15.1%) SLE patients, with 3 (5.6%) having normal NFC pattern and 5 (9.4%) having scleroderma pattern. All controls (n = 20) showed normal hairpin shape capillaries. Except for SLEDAI (P = 0.03) and the presence of RP (P < 0.0001), there were no significant differences in demographic and laboratory parameters between the three NFC patterns (normal, non-specific, and scleroderma); additionally, NFC score correlated significantly with SLEDAI (P = 0.021).

Conclusion

As a result of the high disease activity, Egyptian SLE patients had elevated serum levels of IL 17A and IFNs I. The most common NFC pattern in Egyptian SLE patients was a non-specific pattern. NFC abnormalities in Egyptian SLE patients were correlated with disease activity but not with patients’ ages, disease duration, or serum levels of IL 17A and IFNs I. SLE patients with scleroderma NFC pattern and RP should be closely followed for the possibility of appearance of anti-U1 RNP antibodies and MCTDS.
Retrospective study of acupuncture treatment for canine thoracolumbar intervertebral disc herniation
Authors: Jia Qianyu , Wang Yu , Pang Haidong , Fan Kai , Xie Huisheng , Lin Jiahao
Published: September 2023

Thoracolumbar interverbal disk herniation (TL-IVDH) is a common neurological disorder in dogs, which often affects the life quality of patients and their caregivers. Acupuncture is increasingly accepted by veterinarians and animal owners, and has been used in the treatment of neurologic disorders. This study aims to evaluate the effects of acupuncture treatment for canine TL-IVDH. Clinical cases from 2016 to 2021 were collected. According to the inclusion and exclusion criteria, 94 TL-IVDH cases that received acupuncture treatment were selected. Clinical classification and efficacy criteria were formulated based on the Frankel Score. For each case, clinical presentation, improvement, recovery and recurrence were recorded. Male dogs with TL-IVDH accounted for 64% of all cases. The average age was 7.49 years old, the predominant breed was poodle, and the incidence site was concentrated from T11 to L1. The overall recovery rate after receiving acupuncture treatment was 79.78%, which was comparable when considering only cases with grade 2, 3, or 4 spinal cord lesions (83.33% ~ 85.19%). In conclusion, canine with grade 2, 3, and 4 spinal cord lesions due to TL-IVDH receiving acupuncture had a high recovery rate, suggesting acupuncture could be a viable treatment options for canine with TL-IVDH.