bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of various obturation techniques with bioceramic sealers in 3D-printed C-shaped canals
Authors: Gharechahi Maryam , Hoseinzadeh Melika , Moradi Saeed , Mehrjouei Mina
Published: May 2024

This in vitro study compared various obturation techniques with bioceramic sealers for filling C-shaped 3D-printed replicas. A mandibular molar with a C-shaped root canal with a C1 configuration was obtained. After instrumenting with M3 Pro Gold files (United Dental, Shanghai, China) up to size #30/0.04, a CBCT scan of the tooth was taken. Sixty 3D-printed replicas of the tooth were created. The samples were obturated with EndoSeal TCS sealer (E. TCS; Maruchi, Wonju, Korea) or EndoSeal MTA (E. MTA; Maruchi, Wonju, Korea) (n = 30). The samples in each group were obturated with the following techniques (n = 10): (1) single-cone technique (SC), (2) SC with ultrasonic activation (UA), and (3) cold hydraulic compaction (CHC). Following incubation, the replicas’ apical, middle, and coronal thirds were inspected under a digital microscope, and the proportion of filling material and void were calculated. Also, the obturation time and sealer extrusion were recorded. Data were analyzed using ANOVA, LSD post-hoc, and the chi-square tests (α = 0.05). The results indicated that in the apical third, E. TCS-SC, E. TCS-UA, and E. MTA-UA had the lowest void percentage among groups (p < 0.05). In the middle thirds, samples obturated with E. TCS-UA showed a significantly lower void percentage among all groups (p < 0.05). However, in the coronal third, E. TCS-CHC showed the least void percentage (p < 0.05), followed by E. TCS-UA and E. MTA-CHC. The E. TCS-SC and E. TCS-UA were the least time-consuming methods (p < 0.05). Sealer extrusion significantly differed among the groups, with E. MTA-UA and E. TCS-UA showing higher incidence (p = 0.019). It was concluded that E. TCS-UA was the most convenient obturation technique. However, care must be taken when obturating the canals with high flow and ultrasonic activation near the vital anatomical landmarks.
The role of voltage-gated calcium channel α2δ-1 in the occurrence and development in myofascial orofacial pain
Authors: Lu Yang , Wang Jingfu , Li Li , Zhang Xiaodong
Published: May 2024

Patients who suffer from myofascial orofacial pain could affect their quality of life deeply. The pathogenesis of pain is still unclear. Our objective was to assess Whether Voltage-gated calcium channel α2δ-1(Cavα2δ-1) is related to myofascial orofacial pain. Rats were divided into the masseter tendon ligation group and the sham group. Compared with the sham group, the mechanical pain threshold of the masseter tendon ligation group was reduced on the 4th, 7th, 10th and 14th day after operation(P < 0.05). On the 14th day after operation, Cavα2δ-1 mRNA expression levels in trigeminal ganglion (TG) and the trigeminal spinal subnucleus caudalis and C1-C2 spinal cervical dorsal horn (Vc/C2) of the masseter tendon ligation group were increased (PTG=0.021, PVc/C2=0.012). Rats were divided into three groups. On the 4th day after ligating the superficial tendon of the left masseter muscle of the rats, 10 ul Cavα2δ-1 antisense oligonucleotide, 10 ul Cavα2δ-1 mismatched oligonucleotides and 10 ul normal saline was separately injected into the left masseter muscle of rats in Cavα2δ-1 antisense oligonucleotide group, Cavα2δ-1 mismatched oligonucleotides group and normal saline control group twice a day for 4 days. The mechanical pain threshold of the Cavα2δ-1 antisense oligonucleotides group was higher than Cavα2δ-1 mismatched oligonucleotides group on the 7th and 10th day after operation (P < 0.01). After PC12 cells were treated with lipopolysaccharide, Cavα2δ-1 mRNA expression level increased (P < 0.001). Cavα2δ-1 may be involved in the occurrence and development in myofascial orofacial pain.
Effect of fence tray matching care on excess adhesive and bracket placement accuracy for orthodontic bonding: an in vitro study
Authors: Hu Meichun , Cao Yannan , Wu Xiangbing , Jiang Qian , Zhu Fangyong
Published: May 2024

Objective

This study aimed to evaluate the effect of fence tray matching care (FTMC) in bracket bonding by measuring excess adhesive, as well as linear and angular deviations, and by comparing it with the half-wrapped tray (HWT).

Materials and methods

An intraoral scanner was used to acquire data on the maxillary dental arch of a patient with periodontitis.Furthermore, 20 maxillary dental arch models were 3D printed. Using 3Shape, PlastyCAD software, and 3D printing technology, 10 FTMC (method I) and HWT (method II) were obtained. By preoperative preparation, intraoperative coordination, and postoperative measurement, the brackets were transferred from the trays to the 3D-printed maxillary dental arch models. Additionally, the bracket’s excess adhesive as well as linear and angular deviations were measured, and the differences between the two methods were analyzed.

Results

Excess adhesive was observed in both methods, with FTMC showing less adhesive (P< 0.001), with a statistical difference. Furthermore, HWT’s vertical, tip and torque, which was significantly greater than FTMC (P< 0.05), with no statistical difference among other respects. The study data of incisors, canines, and premolars, showed that the premolars had more adhesive residue and were more likely to have linear and angular deviations.

Conclusions

The FTMC had higher bracket bonding effect in comparison to HWT, and the adhesive residue, linear and angular deviations are smaller. The fence tray offers an intuitive view of the precise bonding of the bracket, and can remove excess adhesive to prevent white spot lesions via care, providing a different bonding method for clinical applications.
Advances and prospects in microbial production of biotin
Authors: Ma Donghan , Du Guangqing , Fang Huan , Li Rong , Zhang Dawei
Published: May 2024

Biotin, serving as a coenzyme in carboxylation reactions, is a vital nutrient crucial for the natural growth, development, and overall well-being of both humans and animals. Consequently, biotin is widely utilized in various industries, including feed, food, and pharmaceuticals. Despite its potential advantages, the chemical synthesis of biotin for commercial production encounters environmental and safety challenges. The burgeoning field of synthetic biology now allows for the creation of microbial cell factories producing bio-based products, offering a cost-effective alternative to chemical synthesis for biotin production. This review outlines the pathway and regulatory mechanism involved in biotin biosynthesis. Then, the strategies to enhance biotin production through both traditional chemical mutagenesis and advanced metabolic engineering are discussed. Finally, the article explores the limitations and future prospects of microbial biotin production. This comprehensive review not only discusses strategies for biotin enhancement but also provides in-depth insights into systematic metabolic engineering approaches aimed at boosting biotin production.
Hesitancy towards R21/Matrix-M malaria vaccine among Ghanaian parents and attitudes towards immunizing non-eligible children: a cross-sectional survey
Authors: Hussein Mohamed Fakhry , Kyei-Arthur Frank , Saleeb Marina , Kyei-Gyamfi Sylvester , Abutima Theophilus , Sakada Ignatius Great , Ghazy Ramy Mohamed
Published: May 2024

Background

The newly developed malaria vaccine called “R21/Matrix-M malaria vaccine” showed a high safety and efficacy level, and Ghana is the first country to approve this new vaccine. The present study aimed to evaluate the rate of vaccine hesitancy (VH) towards the newly developed malaria vaccine among parents who currently have children who are not eligible for the vaccine but may be eligible in the near future. Additionally, the study aimed to identify the factors that could potentially influence VH.

Methods

A cross-sectional survey using both online-based questionnaires and face-to-face interviews was conducted in Ghana from June to August 2023. The survey specifically targeted parents of ineligible children for vaccination, including those aged less than 5 months or between 3 and 12 years. The Parent Attitudes about Childhood Vaccination (PACV) scale was used to assess parental VH.

Results

A total of 765 people participated in this study. Their median age was 36.0 years with an interquartile range of 31.0–41.0 years, 67.7% were females, 41.8% completed their tertiary education, 63.3% were married, 81.6% worked in non-healthcare sectors, and 59.7% reported that their monthly income was insufficient. About one-third (34.5%) of the parents were hesitant to give their children the R21/Matrix-M malaria vaccine. The following predictors were associated with VH: working in the healthcare sector (adjusted odds ratio (AOR) = 0.50; 95% confidence interval (CI) 0.30–0.80; p = 0.005), having the other parent working in the healthcare sector (AOR = 0.54; 95% CI 0.30–0.94; p = 0.034), and not taking scheduled routine vaccinations (AOR = 1.90; 95% CI 1.27–2.84; p = 0.002).

Conclusions

Addressing VH is crucial for optimizing R21/Matrix-M vaccine coverage in Ghana's malaria control strategy. By tackling VH issues, Ghana can effectively safeguard children's health in malaria-prone areas.
Prevalence of malaria and associated risk factors among household members in South Ethiopia: a multi-site cross-sectional study
Authors: Yutura Girma , Massebo Fekadu , Eligo Nigatu , Kochora Abena , Wegayehu Teklu
Published: May 2024

Background

Despite continuous prevention and control strategies in place, malaria remains a major public health problem in sub-Saharan Africa including Ethiopia. Moreover, prevalence of malaria differs in different geographical settings and epidemiological data were inadequate to assure disease status in the study area. This study was aimed to determine the prevalence of malaria and associated risk factors in selected rural kebeles in South Ethiopia.

Methods

A community-based cross-sectional study was conducted between February to June 2019 in eight malaria-endemic kebeles situated in four zones in South Ethiopia. Mult-stage sampling techniques were employed to select the study zones, districts, kebeles and households. Blood sample were collected from 1674 participants in 345 households by finger prick and smears were examined by microscopy. Sociodemographic data as well as risk factors for Plasmodium infection were collected using questionnaires. Bivariate and multivariate logistic regressions were used to analyse the data.

Results

The overall prevalence of malaria in the study localities was 4.5% (76/1674). The prevalence was varied among the study localities with high prevalence in Bashilo (14.6%; 33/226) followed by Mehal Korga (12.1%; 26/214). Plasmodium falciparum was the dominant parasite accounted for 65.8% (50/76), while Plasmodium vivax accounted 18.4% (14/76). Co-infection of P. falciparum and P. vivax was 15.8% (12/76). Among the three age groups prevalence was 7.8% (27/346) in age less than 5 years and 7.5% (40/531) in 5–14 years. The age groups > 14years were less likely infected with Plasmodium parasite (AOR = 0.14, 95% CI 0.02–0.82) than under five children. Non-febrile individuals 1638 (97.8%) were more likely to had Plasmodium infection (AOR = 28.4, 95% CI 011.4–70.6) than febrile 36 (2.2%). Individuals living proximity to mosquito breeding sites have higher Plasmodium infection (AOR = 6.17, 95% CI 2.66–14.3) than those at distant of breeding sites.

Conclusions

Malaria remains a public health problem in the study localities. Thus, malaria prevention and control strategies targeting children, non-febrile cases and individuals living proximity to breeding sites are crucial to reduce malaria related morbidity and mortality.
A portable transistor immunosensor for fast identification of porcine epidemic diarrhea virus
Authors: Hu Xiao , Zhang Mengjia , Liu Yiwei , Li Yu-Tao , Li Wentao , Li Tingxian , Li Jiahao , Xiao Xueqian , He Qigai , Zhang Zhi-Yong , Zhang Guo-Jun
Published: May 2024

Widespread distribution of porcine epidemic diarrhea virus (PEDV) has led to catastrophic losses to the global pig farming industry. As a result, there is an urgent need for rapid, sensitive and accurate tests for PEDV to enable timely and effective interventions. In the present study, we develop and validate a floating gate carbon nanotubes field-effect transistor (FG CNT-FET)-based portable immunosensor for rapid identification of PEDV in a sensitive and accurate manner. To improve the affinity, a unique PEDV spike protein-specific monoclonal antibody is prepared by purification, and subsequently modified on FG CNT-FET sensor to recognize PEDV. The developed FET biosensor enables highly sensitive detection (LoD: 8.1 fg/mL and 100.14 TCID50/mL for recombinant spike proteins and PEDV, respectively), as well as satisfactory specificity. Notably, an integrated portable platform consisting of a pluggable FG CNT-FET chip and a portable device can discriminate PEDV positive from negative samples and even identify PEDV and porcine deltacoronavirus within 1 min with 100% accuracy. The portable sensing platform offers the capability to quickly, sensitively and accurately identify PEDV, which further points to a possibility of point of care (POC) applications of large-scale surveillance in pig breeding facilities.
Aptamer-functionalized nanomaterials (AFNs) for therapeutic management of hepatocellular carcinoma
Authors: Yin Xiujuan , Rong Jing , Shao Min , Zhang Saisai , Yin Likang , He Zhenqiang , Wang Xiao
Published: May 2024

Hepatocellular carcinoma (HCC) represents one of the deadliest cancers globally, making the search for more effective diagnostic and therapeutic approaches particularly crucial. Aptamer-functionalized nanomaterials (AFNs), an innovative nanotechnology, have paved new pathways for the targeted diagnosis and treatment of HCC. Initially, we outline the epidemiological background of HCC and the current therapeutic challenges. Subsequently, we explore in detail how AFNs enhance diagnostic and therapeutic efficiency and reduce side effects through the specific targeting of HCC cells and the optimization of drug delivery. Furthermore, we address the challenges faced by AFNs in clinical applications and future research directions, with a particular focus on enhancing their biocompatibility and assessing long-term effects. In summary, AFNs represent an avant-garde therapeutic approach, opening new avenues and possibilities for the diagnosis and treatment of HCC.

Graphical Abstract
Ti3C2 nanosheet-induced autophagy derails ovarian functions
Authors: Yang Limei , He Zhiting , Hu Le , Tang Hongyu , Geng Yanqing , Tan Qiaoyan , Zhang Yue , Wen Yixian , Wu Wei , Gu Huayan , Liu Xueqing
Published: May 2024

Background

Two-dimensional ultrathin Ti3C2 (MXene) nanosheets have gained significant attention in various biomedical applications. Although previous studies have described the accumulation and associated damage of Ti3C2 nanosheets in the testes and placenta. However, it is currently unclear whether Ti3C2 nanosheets can be translocated to the ovaries and cause ovarian damage, thereby impairing ovarian functions.

Results

We established a mouse model with different doses (1.25, 2.5, and 5 mg/kg bw/d) of Ti3C2 nanosheets injected intravenously for three days. We demonstrated that Ti3C2 nanosheets can enter the ovaries and were internalized by granulosa cells, leading to a decrease in the number of primary, secondary and antral follicles. Furthermore, the decrease in follicles is closely associated with higher levels of FSH and LH, as well as increased level of E2 and P4, and decreased level of T in mouse ovary. In further studies, we found that exposure toTi3C2 nanosheets increased the levels of Beclin1, ATG5, and the ratio of LC3II/Ι, leading to autophagy activation. Additionally, the level of P62 increased, resulting in autophagic flux blockade. Ti3C2 nanosheets can activate autophagy through the PI3K/AKT/mTOR signaling pathway, with oxidative stress playing an important role in this process. Therefore, we chose the ovarian granulosa cell line (KGN cells) for in vitro validation of the impact of autophagy on the hormone secretion capability. The inhibition of autophagy initiation by 3-Methyladenine (3-MA) promoted smooth autophagic flow, thereby partially reduced the secretion of estradiol and progesterone by KGN cells; Whereas blocking autophagic flux by Rapamycin (RAPA) further exacerbated the secretion of estradiol and progesterone in cells.

Conclusion

Ti3C2 nanosheet-induced increased secretion of hormones in the ovary is mediated through the activation of autophagy and impairment of autophagic flux, which disrupts normal follicular development. These results imply that autophagy dysfunction may be one of the underlying mechanisms of Ti3C2-induced damage to ovarian granulosa cells. Our findings further reveal the mechanism of female reproductive toxicity induced by Ti3C2 nanosheets.
MSC microvesicles loaded G-quadruplex-enhanced circular single-stranded DNA-9 inhibits tumor growth by targeting MDSCs
Authors: Han Jingxia , Qin Rong , Zheng Shaoting , Hou Xiaohui , Wang Xiaorui , An Huihui , Li Zhongwei , Li Yinan , Zhang Heng , Zhai Denghui , Liu Huijuan , Meng Jing , Sun Tao
Published: May 2024

Background

Myeloid-derived suppressor cells (MDSCs) promote tumor growth, metastasis, and lead to immunotherapy resistance. Studies revealed that miRNAs are also expressed in MDSCs and promote the immunosuppressive function of MDSCs. Currently, few studies have been reported on inducible cellular microvesicle delivery of nucleic acid drugs targeting miRNA in MDSCs for the treatment of malignant tumors.

Results and conclusion

In this study, we designed an artificial DNA named G-quadruplex-enhanced circular single-stranded DNA-9 (G4-CSSD9), that specifically adsorbs the miR-9 sequence. Its advanced DNA folding structure, rich in tandem repeat guanine (G-quadruplex), also provides good stability. Mesenchymal stem cells (MSCs) were prepared into nanostructured vesicles by membrane extrusion. The MSC microvesicles-encapsulated G4-CSSD9 (MVs@G4-CSSD9) was delivered into MDSCs, which affected the downstream transcription and translation process, and reduced the immunosuppressive function of MDSCs, so as to achieve the purpose of treating melanoma. In particular, it provides an idea for the malignant tumor treatment.

Graphical Abstract
Taking SCFAs produced by Lactobacillus reuteri orally reshapes gut microbiota and elicits antitumor responses
Authors: Li Nannan , Niu Lili , Liu Yao , Wang Yang , Su Xiaomin , Xu Ce , Sun Zanya , Guo Huishu , Gong Jingru , Shen Shun
Published: May 2024

Background

Colorectal cancer (CRC) incidence is increasing in recent years due to intestinal flora imbalance, making oral probiotics a hotspot for research. However, numerous studies related to intestinal flora regulation ignore its internal mechanisms without in-depth research.

Results

Here, we developed a probiotic microgel delivery system (L.r@(SA-CS)2) through the layer-by-layer encapsulation technology of alginate (SA) and chitosan (CS) to improve gut microbiota dysbiosis and enhance anti-tumor therapeutic effect. Short chain fatty acids (SCFAs) produced by L.r have direct anti-tumor effects. Additionally, it reduces harmful bacteria such as Proteobacteria and Fusobacteriota, and through bacteria mutualophy increases beneficial bacteria such as Bacteroidota and Firmicutes which produce butyric acid. By binding to the G protein-coupled receptor 109A (GPR109A) on the surface of colonic epithelial cells, butyric acid can induce apoptosis in abnormal cells. Due to the low expression of GPR109A in colon cancer cells, MK-6892 (MK) can be used to stimulate GPR109A. With increased production of butyrate, activated GPR109A is able to bind more butyrate, which further promotes apoptosis of cancer cells and triggers an antitumor response.

Conclusion

It appears that the oral administration of L.r@(SA-CS)2 microgels may provide a treatment option for CRC by modifying the gut microbiota.
Electrical aligned polyurethane nerve guidance conduit modulates macrophage polarization and facilitates immunoregulatory peripheral nerve regeneration
Authors: Sun Yiting , Zhang Yinglong , Guo Yibo , He Dongming , Xu Wanlin , Fang Wei , Zhang Chenping , Zuo Yi , Zhang Zhen
Published: May 2024

Biomaterials can modulate the local immune microenvironments to promote peripheral nerve regeneration. Inspired by the spatial orderly distribution and endogenous electric field of nerve fibers, we aimed to investigate the synergistic effects of electrical and topological cues on immune microenvironments of peripheral nerve regeneration. Nerve guidance conduits (NGCs) with aligned electrospun nanofibers were fabricated using a polyurethane copolymer containing a conductive aniline trimer and degradable L-lysine (PUAT). In vitro experiments showed that the aligned PUAT (A-PUAT) membranes promoted the recruitment of macrophages and induced their polarization towards the pro-healing M2 phenotype, which subsequently facilitated the migration and myelination of Schwann cells. Furthermore, NGCs fabricated from A-PUAT increased the proportion of pro-healing macrophages and improved peripheral nerve regeneration in a rat model of sciatic nerve injury. In conclusion, this study demonstrated the potential application of NGCs in peripheral nerve regeneration from an immunomodulatory perspective and revealed A-PUAT as a clinically-actionable strategy for peripheral nerve injury.
Cost effectiveness and decision analysis for national airport screening options to reduce risk of COVID-19 introduction in Uganda, 2020
Authors: Amanya Geofrey , Washington Michael L. , Kadobera Daniel , Richard Migisha , Ndyabakiira Alex , Harris Julie
Published: May 2024

Introduction

Early during the COVID-19 outbreak, various approaches were utilized to prevent COVID-19 introductions from incoming airport travellers. However, the costs and effectiveness of airport-specific interventions have not been evaluated.

Methods

We evaluated policy options for COVID-19-specific interventions at Entebbe International Airport for costs and impact on COVID-19 case counts, we took the government payer perspective. Policy options included; (1)no screening, testing, or mandatory quarantine for any incoming traveller; (2)mandatory symptom screening for all incoming travellers with RT-PCR testing only for the symptomatic and isolation of positives; and (3)mandatory 14-day quarantine and one-time testing for all, with 10-day isolation of persons testing positive. We calculated incremental cost-effectiveness ratios (ICERs) in US$ per additional case averted.

Results

Expected costs per incoming traveller were $0 (Option 1), $19 (Option 2), and $766 (Option 3). ICERs per case averted were $257 for Option 2 (which averted 4,948 cases), and $10,139 for Option 3 (which averted 5,097 cases) compared with Option I. Two-week costs were $0 for Option 1, $1,271,431 Option 2, and $51,684,999 Option 3. The per-case ICER decreased with increase in prevalence. The cost-effectiveness of our interventions was modestly sensitive to the prevalence of COVID-19, diagnostic test sensitivity, and testing costs.

Conclusion

Screening all incoming travellers, testing symptomatic persons, and isolating positives (Option 2) was the most cost-effective option. A higher COVID-19 prevalence among incoming travellers increased cost-effectiveness of airport-specific interventions. This model could be used to evaluate prevention options at the airport for COVID-19 and other infectious diseases with similar requirements for control.
The impact of the world’s first regulatory, multi-setting intervention on sedentary behaviour among children and adolescents (ENERGISE): a natural experiment evaluation
Authors: Li Bai , Valerino-Perea Selene , Zhou Weiwen , Xie Yihong , Syrett Keith , Peters Remco , He Zouyan , Zou Yunfeng , de Vocht Frank , Foster Charlie
Published: May 2024

Background

Regulatory actions are increasingly used to tackle issues such as excessive alcohol or sugar intake, but such actions to reduce sedentary behaviour remain scarce. World Health Organization (WHO) guidelines on sedentary behaviour call for system-wide policies. The Chinese government introduced the world’s first nation-wide multi-setting regulation on multiple types of sedentary behaviour in children and adolescents in July 2021. This regulation restricts when (and for how long) online gaming businesses can provide access to pupils; the amount of homework teachers can assign to pupils according to their year groups; and when tutoring businesses can provide lessons to pupils. We evaluated the effect of this regulation on sedentary behaviour safeguarding pupils.

Methods

With a natural experiment evaluation design, we used representative surveillance data from 9- to 18-year-old pupils before and after the introduction of the regulation, for longitudinal (n = 7,054, matched individuals, primary analysis) and repeated cross-sectional (n = 99,947, exploratory analysis) analyses. We analysed pre-post differences for self-reported sedentary behaviour outcomes (total sedentary behaviour time, screen viewing time, electronic device use time, homework time, and out-of-campus learning time) using multilevel models, and explored differences by sex, education stage, residency, and baseline weight status.

Results

Longitudinal analyses indicated that pupils had reduced their mean total daily sedentary behaviour time by 13.8% (95% confidence interval [CI]: -15.9 to -11.7%, approximately 46 min) and were 1.20 times as likely to meet international daily screen time recommendations (95% CI: 1.01 to 1.32) one month after the introduction of the regulation compared to the reference group (before its introduction). They were on average 2.79 times as likely to meet the regulatory requirement on homework time (95% CI: 2.47 to 3.14) than the reference group and reduced their daily total screen-viewing time by 6.4% (95% CI: -9.6 to -3.3%, approximately 10 min). The positive effects were more pronounced among high-risk groups (secondary school and urban pupils who generally spend more time in sedentary behaviour) than in low-risk groups (primary school and rural pupils who generally spend less time in sedentary behaviour). The exploratory analyses showed comparable findings.

Conclusions

This regulatory intervention has been effective in reducing total and specific types of sedentary behaviour among Chinese children and adolescents, with the potential to reduce health inequalities. International researchers and policy makers may explore the feasibility and acceptability of implementing regulatory interventions on sedentary behaviour elsewhere.
Multi-omics integration highlights the role of ubiquitination in endometriosis fibrosis
Authors: Yang Mengjie , Jiang Hong , Ding Xinyu , Zhang Lu , Zhang Huaying , Chen Jiahao , Li Lijun , He Xinqin , Huang Zhixiong , Chen Qionghua
Published: May 2024

Background

Endometriosis, characterized by the presence of active endometrial-like tissues outside the uterus, causes symptoms like dysmenorrhea and infertility due to the fibrosis of endometrial cells, which involves excessive deposition of extracellular matrix (ECM) proteins. Ubiquitination, an important post-transcriptional modification, regulates various biological processes in human diseases. However, its role in the fibrosis process in endometriosis remains unclear.

Methods

We employed multi-omics approaches on two cohorts of endometriosis patients with 39 samples. GO terms and KEGG pathways enrichment analyses were used to investigate the functional changes involved in endometriosis. Pearson’s correlation coefficient analysis was conducted to explore the relationship between global proteome and ubiquitylome in endometriosis. The protein expression levels of ubiquitin-, fibrosis-related proteins, and E3 ubiquitin-protein ligase TRIM33 were validated via Western blot. Transfecting human endometrial stroma cells (hESCs) with TRIM33 small interfering RNA (siRNA) in vitro to explore how TRIM33 affects fibrosis-related proteins.

Results

Integration of proteomics and transcriptomics showed genes with concurrent change of both mRNA and protein level which involved in ECM production in ectopic endometria. Ubiquitylomics distinguished 1647 and 1698 ubiquitinated lysine sites in the ectopic (EC) group compared to the normal (NC) and eutopic (EU) groups, respectively. Further multi-omics integration highlighted the essential role of ubiquitination in key fibrosis regulators in endometriosis. Correlation analysis between proteome and ubiquitylome showed correlation coefficients of 0.32 and 0.36 for ubiquitinated fibrosis proteins in EC/NC and EC/EU groups, respectively, indicating positive regulation of fibrosis-related protein expression by ubiquitination in ectopic lesions. We identified ubiquitination in 41 pivotal proteins within the fibrosis-related pathway of endometriosis. Finally, the elevated expression of TGFBR1/α-SMA/FAP/FN1/Collagen1 proteins in EC tissues were validated across independent samples. More importantly, we demonstrated that both the mRNA and protein levels of TRIM33 were reduced in endometriotic tissues. Knockdown of TRIM33 promoted TGFBR1/p-SMAD2/α-SMA/FN1 protein expressions in hESCs but did not significantly affect Collagen1/FAP levels, suggesting its inhibitory effect on fibrosis in vitro.

Conclusions

This study, employing multi-omics approaches, provides novel insights into endometriosis ubiquitination profiles and reveals aberrant expression of the E3 ubiquitin ligase TRIM33 in endometriotic tissues, emphasizing their critical involvement in fibrosis pathogenesis and potential therapeutic targets.
An electrophoretic mobility shift assay using the protein isolated from host plants
Authors: He Zihang , Wang Zhibo , Lu Zhangguo , Gao Caiqiu , Wang Yucheng
Published: May 2024

Background

The electrophoretic mobility shift assay (EMSA) is a common technology to detect DNA-protein interactions. However, in most cases, the protein used in EMSA is obtained via prokaryotic expression, and rarely from plants. At the same time, the proteins expressed from prokaryotic systems usually cannot fold naturally and have no post translationally modification, which may affect the binding of proteins to DNA.

Results

Here, we develop a technique to quickly isolate proteins of interest from host plants and then analyze them using fluorescent EMSA. This technology system is called: protein from plants fluorescent EMSA method (PPF-EMSA). In PPF-EMSA, a special transient transformation method is employed to transiently deliver genes into the plant, enabling efficient synthesis the encoded proteins. Then, the target protein is isolated using immunoprecipitation, and the DNA probes were labeled with cyanine 3 (Cy3). Both fluorescent EMSA and super-shift fluorescent EMSA can be performed using the proteins from plants. Three kinds of plants, Betula platyphylla, Populus. davidiana×P. bolleana and Arabidopsis thaliana, are used in this study. The proteins isolated from plants are in a natural state, can fold naturally and are posttranslationally modified, enabling true binding to their cognate DNAs.

Conclusion

As transient transformation can be performed quickly and not depended on whether stable transformation is available or not, we believe this method will have a wide application, enabling isolation of proteins from host plant conveniently.
Accurate object localization facilitates automatic esophagus segmentation in deep learning
Authors: Li Zhibin , Gan Guanghui , Guo Jian , Zhan Wei , Chen Long
Published: May 2024

Background

Currently, automatic esophagus segmentation remains a challenging task due to its small size, low contrast, and large shape variation. We aimed to improve the performance of esophagus segmentation in deep learning by applying a strategy that involves locating the object first and then performing the segmentation task.

Methods

A total of 100 cases with thoracic computed tomography scans from two publicly available datasets were used in this study. A modified CenterNet, an object location network, was employed to locate the center of the esophagus for each slice. Subsequently, the 3D U-net and 2D U-net_coarse models were trained to segment the esophagus based on the predicted object center. A 2D U-net_fine model was trained based on the updated object center according to the 3D U-net model. The dice similarity coefficient and the 95% Hausdorff distance were used as quantitative evaluation indexes for the delineation performance. The characteristics of the automatically delineated esophageal contours by the 2D U-net and 3D U-net models were summarized. Additionally, the impact of the accuracy of object localization on the delineation performance was analyzed. Finally, the delineation performance in different segments of the esophagus was also summarized.

Results

The mean dice coefficient of the 3D U-net, 2D U-net_coarse, and 2D U-net_fine models were 0.77, 0.81, and 0.82, respectively. The 95% Hausdorff distance for the above models was 6.55, 3.57, and 3.76, respectively. Compared with the 2D U-net, the 3D U-net has a lower incidence of delineating wrong objects and a higher incidence of missing objects. After using the fine object center, the average dice coefficient was improved by 5.5% in the cases with a dice coefficient less than 0.75, while that value was only 0.3% in the cases with a dice coefficient greater than 0.75. The dice coefficients were lower for the esophagus between the orifice of the inferior and the pulmonary bifurcation compared with the other regions.

Conclusion

The 3D U-net model tended to delineate fewer incorrect objects but also miss more objects. Two-stage strategy with accurate object location could enhance the robustness of the segmentation model and significantly improve the esophageal delineation performance, especially for cases with poor delineation results.
Epidemiological investigation and diagnostic analysis of osteonecrosis of the femoral head in three northeastern provinces of China
Authors: Liu Wangyan , Yue Ju’an , Guo Xiaozhong , Wang Randong , Fu Hao
Published: May 2024

Background

In this retrospective case investigation, we analysed the data of patients with osteonecrosis of the femoral head (ONFH) to reveal demographic and clinical diagnostic features of ONFH in three northeastern provinces of China and provide a reference for its prevention, diagnosis, and treatment.

Methods

We collected data from patients in Beijing Orthopaedic Hospital of Liaoning, focusing on the aetiology and diagnosis of ONFH. Medical records and self-designed questionnaires were used to collect information for statistical analysis, including age, aetiology, reason for glucocorticoid use, hospital level at first visit, and diagnosis.

Results

In total, 906 patients with complete medical records were included in the analysis. The mean patient age was 47.65 ± 12.12 years. The peak age distribution was in the 40s for men and the 50s for women. Among the total cohort, 72 patients (7.95%; 40 men and 32 women) had traumatic ONFH, 198 (21.85%; 131 men and 67 women) had steroid-induced ONFH, 230 (25.39%; 121 men and 109 women) had idiopathic ONFH, and 406 (44.81%; 397 men and 9 women) had alcohol-induced ONFH. Six hundred and twenty patients were diagnosed with ONFH at the first visit, while 286 patients were misdiagnosed, with a diagnosis rate of 68.43%. The diagnosis rate at the first visit in tertiary hospitals was 76.14%. The diagnosis rate at the first visit in second-class hospitals was 52.07%.ONFH was most likely to be misdiagnosed as lumbar disc herniation.

Conclusions

Most patients with ONFH in three northeastern provinces of China were middle-aged, male, and had alcohol-induced ONFH. The misdiagnosis rate of ONFH at the first visit was very high, especially for misdiagnosis of lumbar disc herniation, indicating that the diagnosis of ONFH requires further improvement.
Biomechanical changes in the proximal femur before and after removal of femoral neck system
Authors: Nan Chong , Liu Yuxiu , Zhang Di , Qin Yazhuo , Yu Hetong , Ma Zhanbei
Published: May 2024

Background

As an innovative internal fixation system, FNS (femoral neck system) is increasingly being utilized by surgeons for the treatment of femoral neck fractures. At present, there have been numerous finite element analysis experiments studying the immediate stability of FNS and CSS in treating femoral neck fractures. However, there is scarce mechanical analysis available regarding the effects post internal fixation removal. This study aimed to investigate the alterations in mechanical parameters of the proximal femur before and after the removal of FNS (femoral neck system), and to assess potential distinctions in indicators following the extraction of CSS (Cannulated Screws).

Methods

A proximal femur model was reconstructed using finite element numerical techniques. The models for CSS and FNS were formulated utilizing characteristics and parametric definitions. The internal fixation was combined with a normal proximal femur model to simulate the healing state after fracture surgery. Within the framework of static analysis, consistent stress burdens were applied across the entirety of the models. The total deformation and equivalent stress of the proximal femur were recorded before and after the removal of internal fixation.

Results

Under the standing condition, the total deformation of the model before and after removing CSS was 0.99 mm and 1.10 mm, respectively, indicating an increase of 12%. The total deformation of the model before and after removing FNS was 0.65 mm and 0.76 mm, respectively, indicating an increase of 17%. The equivalent stress for CSS and FNS were 55.21 MPa and 250.67 MPa, respectively. The average equivalent stress on the cross-section of the femoral neck before and after removal of CSS was 7.76 MPa and 6.11 MPa, respectively. The average equivalent stress on the cross-section of the femoral neck before and after removal of FNS was 9.89 MPa and 8.79 MPa, respectively.

Conclusions

The retention of internal fixation may contribute to improved stability of the proximal femur. However, there still existed risks of stress concentration in internal fixation and stress shielding in the proximal femur. Compared to CSS, the removal of FNS results in larger bone tunnels and insufficient model stability. Further clinical interventions are recommended to address this issue.
Do nutritional assessment tools (PNI, CONUT, GNRI) predict adverse events after spinal surgeries? A systematic review and meta-analysis
Authors: Huang Zhi , Wang Hanbo , Da Yifeng , Liu Shengxiang , Zheng Wenkai , Li Feng
Published: May 2024

Background

Nutritional assessment tools are used to predict outcomes in cancer. However, their utility in patients undergoing spinal surgery is unclear. This review examined if prognostic nutritional index (PNI), controlling nutritional status (CONUT), and geriatric nutritional risk index (GNRI) can predict adverse events after spinal surgeries.

Methods

PubMed, CENTRAL, Scopus, and Embase were screened by two reviewers for relevant studies up to 26th January 2024. The primary outcome of interest was total adverse events after spinal surgery. Secondary outcomes were surgical site infections (SSI) and mortality.

Results

14 studies were included. Meta-analysis showed that while reduced PNI was not associated with an increased risk of SSI there was a significant association between PNI and higher risk of adverse events. Meta-analysis showed that high CONUT was not associated with an increased risk of complications after spinal surgeries. Pooled analysis showed that low GNRI was associated with an increased risk of both SSI and adverse events. Data on mortality was scarce.

Conclusions

The PNI and GNRI can predict adverse outcomes after spinal surgeries. Limited data shows that high CONUT is also associated with a non-significant increased risk of adverse outcomes. High GNRI was predictive of an increased risk of SSI. Data on mortality is too scarce for strong conclusions.
The effect of long-term alendronic acid treatment on Modic changes in the lumbar spine: a gender and age-matched study
Authors: Yiu Kenneth , Ahn Hyunjeong , Shea Graham Ka-Hon
Published: May 2024

Background

Low back pain (LBP) affects a significant proportion of the adult population. Potent anti-resorptive drugs such as intravenous zoledronic acid have been demonstrated to reduce Modic changes (MCs) upon magnetic resonance imaging (MRI) of the spine and concomitantly decrease associated LBP. It is uncertain whether oral alendronic acid has a similar effect.

Methods

82 subjects were recruited in this case-control study. Treatment subjects (n = 41) received oral alendronic acid treatment for at least 1-year and were matched by gender and age (± 2) to control subjects (n = 41) not receiving any anti-osteoporotic medication. The prevalence, type, and extent of MCs were quantified upon T1 and T2-weighted MRIs of the lumbosacral spine.

Results

Treatment subjects received oral alendronic acid for 124.0 ± 62.1 weeks at the time of MRI assessment and exhibited a lower prevalence of MCs over the lumbosacral spine (18/41 vs. 30/41, p < 0.001) as compared to control subjects. Amongst both groups, type 2 MCs were predominant. Quantification of type 2 MCs in treatment subjects revealed a significant reduction in area (113 ± 106 mm2 vs. 231 ± 144 mm2, p < 0.01) and volume (453 ± 427 mm3 vs. 925 ± 575 mm3, p < 0.01) affected by type 2 MCs in comparison to matched controls.

Conclusion

Oral alendronic acid may be useful in the treatment of MC-associated LBP in patients with concomitant osteoporosis.
Factors that influence in-brace derotation effects in patients with adolescent idiopathic scoliosis: a study based on EOS imaging system
Authors: Fan Qing , Yang Jingfan , Sha Lin , Yang Junlin
Published: May 2024

Objective

To investigate the effects of bracing on apical vertebral derotation and explore the factors that influence in-brace derotation effects in adolescent idiopathic scoliosis (AIS) patients.

Summary of background data

For patients with AIS, vertebral rotation causes cosmetic appearance abnormalities and acts as an indicator for curve progression. However, there have been few studies investigating the precise derotation effects of bracing for apical vertebra. The application of EOS imaging system enables quantitative evaluation of vertebral rotation in the axial plane in a standing position.

Methods

There were 82 eligible patients enrolled in current study, who underwent EOS imaging evaluation before and immediately after bracing. The clinical demographic data (age, gender, Risser sign and menstrual status) were recorded. The correlation analyses between derotation effects and key parameters (age, pre-brace Cobb angle, thoracic kyphosis, lumbar lordosis, vertebral rotation, pelvis axial rotation and apical vertebral level) were performed. The in-brace derotation effects stratified by gender, Risser sign, apical vertebral level, menarche status, coronal balance and sagittal balance were also analyzed.

Results

The rotation of apical vertebra was decreased from 8.8 ± 6.0 degrees before bracing to 3.8 ± 3.3 degrees immediately after bracing (p < 0.001), and the derotation rate was 49.2 ± 38.3%. The derotation degrees in brace was significantly correlated with major curve Cobb angle (r = 0.240, p = 0.030), minor curve Cobb angle (r = 0.256, p = 0.020) and total curve Cobb angle (r = 0.266, p = 0.016). Both the pre-brace apical vertebral rotation and apical vertebral level were significantly correlated with derotation effects in brace (p < 0.001). Patients with thoracic major curve showed worse derotation effects than those with lumbar major curve (p < 0.001). In addition, patients with coronal balance showed better in-brace derotation effects than those with coronal decompensation (p = 0.005).

Conclusions

A satisfactory apical vertebral derotation rate (approximately 50%) could be obtained immediately after bracing in AIS patients. Pre-brace Cobb angle of curve, pre-brace apical vertebral rotation, apical vertebral level and coronal balance exhibited close associations with in-brace derotation effects of apical vertebra.
Incomplete immunization uptake and associated factors among children aged 12–23 months in sub-Saharan African countries; multilevel analysis evidenced from latest demography and health survey data, 2023
Authors: Tsegaw Tigist Kifle , Alemaw Helen Birhan , Wale Yordanos Bitweded , Nigatu Solomon Gedlu , Birhan Tilahun Yemanu , Taddese Asefa Adimasu
Published: May 2024

Background

In 1974, the World Health Organization (WHO) established the Expanded Program on Immunization to control vaccine-preventable diseases, saving millions of lives annually. However, the coverage of basic vaccines recommended by the WHO in Africa was only 75%, which fell short of the goal of 90% by 2015. To formulate effective policies and implementation programs to reduce incomplete vaccination rates, it is important to conduct a study to determine the factors contributing to incomplete immunization among children aged 12–23 months.

Methods

The study was conducted in 16 sub-Saharan African countries, using data extracted from the latest DHS data. It was a community-based cross-sectional survey that used two-stage stratified probability sampling sample designs. The vaccination coverage was assessed using vaccination cards and mother recalls. Multilevel multivariable logistic regression was used to determine the extent of incomplete immunization and the individual and community-level factors associated with partial immunization among children aged 12–23 months. Variables with a p-value less than 0.05 were considered statistically significant predictors of incomplete immunization.

Result

A total of 35, 193 weighted samples were used to determine the pooled prevalence of partial immunization. The pooled prevalence of incomplete immunization was 36.06%. In the final model factors significantly associated were: being uneducated mother(AOR:1.75;95%CI:1.48,2.05), being an unemployed mother (AOR:1.16;95%CI:1.09,1.23), no history of family planning utilization (AOR: 1.71; 95% CI: 1.61, 1.84), non-antenatal care (AOR: 1.79; 95% CI: 1.58, 2.04), non-postnatal care (AOR: 1.25; 95%CI: 1.17, 1.35), rural residence(AOR:1.50;95%CI:1.37,1.63), home delivery (AOR: 2.04; 95%CI:1.89, 2.21), having children more than five (AOR: 1.56; 95%CI: 1.13, 2.17), and non-utilization of health insurance (AOR: 1.74; 95%CI: 1.48, 2.05).

Conclusion

The pooled prevalence of incomplete immunization was found to be high in this investigation. Based on the findings of the study we recommended that policymakers and stakeholders prioritize enhancing prenatal and postnatal care, contraception, and reducing home birth rates to minimize the rate of incomplete immunization.
Best practices for the management of febrile seizures in children
Authors: Ferretti Alessandro , Riva Antonella , Fabrizio Alice , Bruni Oliviero , Capovilla Giuseppe , Foiadelli Thomas , Orsini Alessandro , Raucci Umberto , Romeo Antonino , Striano Pasquale , Parisi Pasquale
Published: May 2024

Febrile seizures (FS) are commonly perceived by healthcare professionals as a self-limited condition with a generally ‘benign’ nature. Nonetheless, they frequently lead to pediatric consultations, and their management can vary depending on the clinical context. For parents and caregivers, witnessing a seizure can be a distressing experience, significantly impacting their quality of life. In this review, we offer an in-depth exploration of FS management, therapeutic interventions, and prognostic factors, with the aim of providing support for physicians and enhancing communication with families. We conducted a comprehensive literature search using the PubMed and Web of Science databases, spanning the past 50 years. The search terms utilized included “febrile seizure,” “complex febrile seizure,” “simple febrile seizure,” in conjunction with “children” or “infant.” Only studies published in English or those presenting evidence-based data were included in our assessment. Additionally, we conducted a cross-reference search to identify any additional relevant data sources. Our thorough literature search resulted in a compilation of references, with carefully selected papers thoughtfully integrated into this review.