bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of primary osteoporosis score (RPOPs): an algorithm model for primary osteoporosis risk assessment in grass-roots hospital
Authors: Jiang Xinhua , Yan Na , Zheng Yaqin , Yang Jintao , Zhao Yanfei
Published: December 2022

Background

This study aimed to develop and validate a lasso regression algorithm model which was established by correlation factors of bone mineral density (BMD) and could be accurately predicted a high-risk population of primary osteoporosis (POP). It provides a rapid, economical and acceptable early screening method for osteoporosis in grass-roots hospitals.

Methods

We collected 120 subjects from primary osteoporosis screening population in Zhejiang Quhua Hospital between May 2021 and November 2021 who were divided into three groups (normal, osteopenia and osteoporosis) according to the BMD T-score. The levels of three micro-RNAs in the plasma of these people were detected and assessed by qRT-PCR. At the same time, the levels of β-CTX and t-P1NP in serum of the three groups were determined. Based on the cluster random sampling method, 84 subjects (84/120, 70%) were selected as the training set and the rest were the test set. Lasso regression was used to screen characteristic variables and establish an algorithm model to evaluate the population at high risk of POP which was evaluated and tested in an independent test cohort. The feature variable screening process was used 10-fold cross validation to find the optimal lambda.

Results

The osteoporosis risk score was established in the training set: Risk of primary osteoporosis score (RPOPs) = -0.1497785 + 2.52Age − 0.19miR21 + 0.35miR182 + 0.17β-CTx. The sensitivity, precision and accuracy of RPOPs in an independent test cohort were 79.17%, 82.61% and 75%, respectively. The AUC in the test set was 0.80. Some risk factors have a significant impact on the abnormal bone mass of the subjects. These risk factors were female (p = 0.00013), older than 55 (p < 2.2e-16) and BMI < 24 (p = 0.0091) who should pay more attention to their bone health.

Conclusion

In this study, we successfully constructed and validated an early screening model of osteoporosis that is able to recognize people at high risk for developing osteoporosis and remind them to take preventive measures. But it is necessary to conduct further external and prospective validation research in large sample size for RPOPs prediction models.
Mechanical effects of sagittal variations on Pauwels type III femoral neck fractures treated with Femoral Neck System(FNS)
Authors: Nan Chong , Ma Liang , Liang Yuechuang , Li Yanjun , Ma Zhanbei
Published: December 2022

Background

The spatial position of internal fixation play a role in determining the stability of internal fixations, both in clinical practice and research. Researchers have examined the stability of FNS (Femoral neck system) in the presence of coronal plane changes. In our knowledge, due to the biomechanical limitations of the specimens, there are no mechanical studies on the sagittal variation of FNS. This study aimed to investigate the biomechanical behavior of sagittal variations on Pauwels type III femoral neck fractures treated with FNS through finite element analysis.

Methods

Finite element models including Pauwels type III femoral neck fracture and FNS were reconstructed. Five fracture models(superior, central, inferior, anterior, posterior) were created in accordance with the bolt location in the sagittal plane within the femoral head. Equivalent stress, shear stress, and total deformation of each model under the same physiological load were recorded.

Results

According to the results, the central model exhibited the slightest stress and displacement, with the exception of the superior model. The internal fixation stress of the superior model was smaller than that of the central model. However, the maximum interfragmentary stress, total deformation and shear resistance area of the superior model was larger than that of the central model.

Conclusions

Central position of FNS in the sagittal plane allowed axial compression while reducing shear stress of internal fixation and interfragmentary equivalent stress. Off-axis fixation of the femoral neck increased the strain area and total displacement of the bone, raising the risk of fixation failure. Therefore, the central placement of FNS may be a better surgical target in the treatment of femoral neck fractures.
Serum periostin level is not sufficient to serve as a clinically applicable biomarker of osteoarthritis
Authors: Tan Qizhao , Yang Zhongwei , Xin Xing , Yang Bin , Xing Zhili , Li Feng , Zhang Ke , Tian Yun , Zhu Tengjiao
Published: December 2022

Background

Emerging knowledge has highlighted the role of periostin (POSTN) in osteoarthritis (OA) process; however, whether POSTN is suitable as a biomarker of OA remains unclear. This study aimed to investigate the potential value of POSTN as a biomarker of OA.

Methods

Ten 6-month-old female Sprague–Dawley (SD) rats were used in this study. Five rats underwent ovariectomy (OVX) operation and the others were carried out sham operation. Thirty-two patients with OA and eighteen patients who had meniscus injuries or ligament injuries but with intact articular cartilages were recruited in this study from January to July 2019 at the Peking University International Hospital. We first detected the expression of POSTN in the cartilage of OVX induced OA rats and different compartments of the knee joint in patients with OA using immunohistochemistry. Besides, serum POSTN levels in patients with or without OA were examined using enzyme-linked immunosorbent assay (ELISA). The associations among serum POSTN levels, clinical symptoms, and radiological severity were assessed according to the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and, Kellgren-Lawrence (KL) grading, respectively. Finally, multivariable cumulative link models were established to evaluate the validity of serum POSTN level as a predictor of knee OA.

Results

The significantly higher POSTN expression was found in OVX-OA rats than Sham rats, while, the expression of POSTN was significantly higher in the torn cartilage of patients with OA. However, the serum POSTN level did not differ significantly between patients with and without OA. Additionally, we found no remarkable associations between serum POSTN level and WOMAC scores and KL grading. Subsequent analysis revealed that serum POSTN was not a significant predictor of OA.

Conclusion

Thus, although POSTN may be involved OA process and local POSTN is valuable in disease diagnosis and distinguishing of the severity of disease, its serum level is not sufficient to serve as a candidate biomarker of OA given the current analysis technology.
Ovarian volume, not follicle count, is independently associated with androgens in patients with polycystic ovary syndrome
Authors: Mansour Asieh , Hashemi Taheri Amir Pejman , Moradi Behnaz , Mohajeri-Tehrani Mohammad Reza , Qorbani Mostafa , Ghorbani Pashakolaee Sahar , Sanginabadi Milad , Sajjadi-Jazi Sayed Mahmoud
Published: December 2022

Background

Polycystic ovary syndrome (PCOS) is diagnosed based on chronic anovulation, androgen excess (clinical and/or biochemical), and polycystic ovaries in ultrasound. The aim of the present study was to evaluate which parameters in the transvaginal ultrasound (TVUS) of ovaries could be better associated with concurrent hormonal imbalance in the women with PCOS.

Methods

Using a cross-sectional design, this study focused on 61 subjects (18–40 years) with PCOS. Patients were recruited at three academic hospitals during the 2017–2019 period. PCOS was defined according to the Rotterdam criteria. The association of ovarian morphology with hormonal and metabolic feature was investigated using linear regression models, adjusted for a set of possible confounding variables including age, mensuration status and body mass index (BMI).

Results

The mean volume of both ovaries was positively associated with the total testosterone level (β = 0.025, P value < 0.001), free androgen index (β = 0.041, P value < 0.001) and luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio (β = 0.032, P value = 0.004), even after adjustments made for age, mensuration status and BMI (fully-adjusted model). In contrast, in the fully-adjusted model, antral follicle count (AFC), follicle number per ovary (FNPO), ovarian area, stromal area, and ratio of stromal area to ovarian area (S/A) were not associated with androgen levels and LH/FSH ratio. In addition, after full adjustments, ovarian volume, AFC, FNPO, ovarian area, stromal area and S/A were not associated with insulin resistance, which was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR).

Conclusion

Increased ovarian volume is, thus, highly predictive of hyperandrogenemia and high LH/FSH ratio in PCOS patients.
Comparison of the 1 and 2% pilocarpine mouthwash in a xerostomic population: a randomized clinical trial
Authors: Motamed Babak , Alaee Arezoo , Azizi Arash , Jahandar Hoda , Fard Mohammad Javad Kharazi , Jafari Aryan
Published: December 2022

Aims & background

Pilocarpine is an accepted treatment for xerostomia, but limited research has been conducted on the oral, topical form. The present study aimed to compare the effects of 1 and 2% pilocarpine mouthwash on xerostomic participants.

Methods

In this double-blind clinical trial study, 48 subjects with xerostomia were randomly divided into three groups to measure the effects of 1 and 2% pilocarpine and placebo mouthwashes on saliva levels. The amount of saliva in the 1st and 14th days was measured at 0, 45, 60, and 75 mins, while participants used their mouthwash three times a day for 14 days. On the 1st and 14th days, they filled out the information forms on xerostomia and the medicine’s side effects before and after the intervention.

Results

On the 1st day, the mean salivary flow at 45, 60, and 75 mins in the 2 and 1% pilocarpine mouthwash were significantly higher than in the placebo mouthwash group (p < 0.05). On the 14th day, the mean salivary flow time at 45 mins in the 2% pilocarpine mouthwash group was significantly higher than in the placebo mouthwash group (p = 0.007). Furthermore, the mean salivary flow at 60 and 75 mins in the 2% (p < 0.001) and 1% pilocarpine mouthwash (p = 0.028) was significantly higher than in the placebo group. Moreover, the salivary flow in the 2% pilocarpine mouthwash group was significantly higher than the 1% pilocarpine mouthwash (p < 0.05) during these two times. No side effects were observed in any of the subjects.

Conclusions

The study showed that 5 ml of 2 and 1% pilocarpine mouthwash for 2 weeks increased salivary flow in xerostomic participants compared to placebo without any side effects.
Oral and para-oral lymphomas: a 10-year multi-center retrospective study in Egypt with time series analysis and forecasting to 2030
Authors: Ashoub Madiha , Wali Mona , Noureldin Nada , Keraa Khaled , El Desouky Eman , Mokbel ElShafei Marwa
Published: December 2022

Background

Little is known about the epidemiology of lymphomas occurring in oral and para-oral sites, especially in developing countries such as Egypt. Hence, the aim of this study was to describe the frequency and time trends of oral and para-oral lymphomas in Cairo governorate from 2010 to 2019, with forecasting to 2030, and to examine relations between age, gender, site and type of lymphoma.

Methods

Histopathological reports of patients diagnosed with oral and para-oral lymphomas from 2010 to 2019 were retrospectively retrieved from archives of six different centers in Cairo governorate. Data regarding age, gender and site was collected and associations between types of lymphoma and these variables were detected using appropriate statistical methods. The significance level was set at p ≤ 0.05. Time series analysis was used to determine the trend of lymphoma frequency within 10 years of the study and to predict frequency until 2030.

Results

Lymphomas constituted 2.86% of oral and para-oral lesions. Non-Hodgkin lymphoma was more common than Hodgkin lymphoma. Patients with non-Hodgkin lymphoma showed a higher median age than patients with Hodgkin lymphoma (p = 0.001). Non-Hodgkin lymphoma was more prone to occur intra-orally (p = 0.014). No statistical significance was observed in gender distribution between Hodgkin and non-Hodgkin lymphoma. Even though no specific time trend was observed from 2010 to 2019, forecasting for frequency of lymphomas through 10 years (2020 to 2030) showed a predicted increase.

Conclusions

The findings of this study were consistent with majority of other studies held in various geographic regions. The study revealed that frequency of oral and para-oral lymphomas in Cairo governorate is expected to rise; hence, oral pathologists should be more clinically suspicious and expect to encounter these lesions more in their practice within the upcoming years.
The dental phenotype of primary dentition in SATB2-associated syndrome: a report of three cases and literature review
Authors: Li Xiaojing , Ye Xiaowei , Su Jimei
Published: December 2022

Background

SATB2-associated syndrome (SAS; OMIM: 612,313) is an autosomal dominant inherited multisystemic disorder caused by several variants of the SATB2 gene. SAS is characterized by intellectual disability, developmental delay, severe speech anomalies, craniofacial anomalies, and dental abnormalities. Here, we report the dental phenotype of primary dentition of three Chinese children with SAS.

Case presentation

All three cases with SAS showed intellectual disability, speech and language anomalies, and palate anomalies. For the dental phenotype, all three cases showed macrodontia, crowded dentition, extensive caries, periapical abscesses and fistulas. Radiographs showed the wide-open root apex of deciduous teeth, loss of mandibular second bicuspids, delayed root formation of permanent teeth, rotated teeth, and taurodontism. Sanger sequencing of case 1 showed that there was a heterozygous code shift variation, c1985delT (p.F662Sfs*9) in the SATB2 gene, which has not been reported in literature. Root canal therapy, carious restoration, and teeth extraction were managed promptly, while preventive dental care was given regularly.

Conclusions

The dental phenotype of primary dentition in SAS may show macrodontia, crowded dentition, severe caries, wide-open root apex of deciduous teeth, loss of mandibular second bicuspids, delayed root formation of permanent teeth, rotated teeth, and taurodontism. Regular oral hygiene instructions and preventive dental care are both required.
Stress distribution in pediatric zirconia crowns depending on different tooth preparation and cement type: a finite element analysis
Authors: Chung Sang-Yeop , Lee Hyeonjong , Chae Yong Kwon , Jung Yun Sun , Jo Su-Sung , Lee Ko Eun , Choi Sung Chul , Nam Ok Hyung
Published: December 2022

Background

In clinical settings, tooth preparation for prefabricated zirconia crowns (PZCs) in the primary dentition varies widely. However, knowledge about the biomechanical behavior of PZCs in various clinical settings is limited. This study was conducted to evaluate the biomechanical behavior of PZCs in different clinical settings using 3-dimensional finite element analysis.

Methods

3-dimensional models of the PZC, cement, and tooth with six different conditions were simulated in primary molar teeth, incorporating cement thickness (100, 500, and 1000 μm) and cement type (resin-modified glass ionomer cement and resin cement). A total of 200 N of occlusal force was applied to the models, both vertically and obliquely as representative cases. A general linear model univariate analysis with partial eta-squared (ηp2) was performed to evaluate the relative effects of the variables.

Results

The overall stress of tooth was increased as the cement space increases under oblique loading. The von Mises stress values of the resin cements were significantly higher than those of the resin-modified glass ionomer cements for all cement thicknesses (p < .05). The effect size of the cement type (ηp2 = .519) was more dominant than the cement thickness (ηp2 = .132) in the cement layer.

Conclusions

Within the limits of this study, cement type has a greater influence on the biomechanical behavior of PZCs than cement thickness.
Facial biotype classification for orthodontic treatment planning using an alternative learning algorithm for tree augmented Naive Bayes
Authors: Ruz Gonzalo A. , Araya-Díaz Pamela , Henríquez Pablo A.
Published: December 2022

Background

When designing a treatment in orthodontics, especially for children and teenagers, it is crucial to be aware of the changes that occur throughout facial growth because the rate and direction of growth can greatly affect the necessity of using different treatment mechanics. This paper presents a Bayesian network approach for facial biotype classification to classify patients’ biotypes into Dolichofacial (long and narrow face), Brachyfacial (short and wide face), and an intermediate kind called Mesofacial, we develop a novel learning technique for tree augmented Naive Bayes (TAN) for this purpose.

Results

The proposed method, on average, outperformed all the other models based on accuracy, precision, recall, $$F_{1}\hbox {-score}$$

F
1

-score

, and kappa, for the particular dataset analyzed. Moreover, the proposed method presented the lowest dispersion, making this model more stable and robust against different runs.

Conclusions

The proposed method obtained high accuracy values compared to other competitive classifiers. When analyzing a resulting Bayesian network, many of the interactions shown in the network had an orthodontic interpretation. For orthodontists, the Bayesian network classifier can be a helpful decision-making tool.
Physiotherapy use is increased for up to nine months after receiving respiratory support for COVID-19
Authors: Skyrud Katrine Damgaard , Huseby Beate Margrethe , Magnusson Karin
Published: December 2022

Aim

To explore whether physiotherapy use is increased after hospitalization with COVID-19 with or without respiratory support vs. other respiratory tract infections (RTI).

Methods

In all Norwegian residents aged 18–80 years who were hospitalized with COVID-19 (N = 5,344) or other RTI (N = 82,235) between July 1st 2017 and August 1st 2021, we used a pre-post study design to explore the weekly individual average physiotherapy use in community care from 12 weeks prior to hospital admission, to 36 weeks (9 months) after hospital discharge for individuals who received and who did not receive respiratory support.

Results

Prior to the hospital stay, COVID-19 patients and patients with other RTI had ~ 40–60 physiotherapist consultations per 1000 inpatients per week. COVID-19 patients on respiratory support had a higher increase in physiotherapy use after discharge than persons with other RTI on respiratory support (an additional 27.3 (95% confidence interval = 10.2 to 44.4) consultations per 1000 for men, and 41.8 (13.7 to 69.9) per 1000 for women)). The increase in physiotherapy use lasted for 6 months for men, and 9 months for women. COVID-19 inpatients without respiratory support had a similar up-to-9-months-change post-discharge physiotherapy use as inpatients with other RTI without respiratory support (-0.2 (-0.7 to 0.2) for men, and 0.09 (-6.4 to 6.6) for women).

Conclusion

The need for physiotherapy was increased for up to 9 months after having COVID-19 requiring respiratory support vs. other RTI requiring respiratory support. No difference between diseases was seen for individuals who were hospitalized but not on respiratory support.
Using phosphoglucose isomerase-deficient (pgi1Δ) Saccharomyces cerevisiae to map the impact of sugar phosphate levels on d-glucose and d-xylose sensing
Authors: Borgström Celina , Persson Viktor C. , Rogova Oksana , Osiro Karen O. , Lundberg Ester , Spégel Peter , Gorwa-Grauslund Marie
Published: December 2022

Background

Despite decades of engineering efforts, recombinant Saccharomyces cerevisiae are still less efficient at converting d-xylose sugar to ethanol compared to the preferred sugar d-glucose. Using GFP-based biosensors reporting for the three main sugar sensing routes, we recently demonstrated that the sensing response to high concentrations of d-xylose is similar to the response seen on low concentrations of d-glucose. The formation of glycolytic intermediates was hypothesized to be a potential cause of this sensing response. In order to investigate this, glycolysis was disrupted via the deletion of the phosphoglucose isomerase gene (PGI1) while intracellular sugar phosphate levels were monitored using a targeted metabolomic approach. Furthermore, the sugar sensing of the PGI1 deletants was compared to the PGI1-wildtype strains in the presence of various types and combinations of sugars.

Results

Metabolomic analysis revealed systemic changes in intracellular sugar phosphate levels after deletion of PGI1, with the expected accumulation of intermediates upstream of the Pgi1p reaction on d-glucose and downstream intermediates on d-xylose. Moreover, the analysis revealed a preferential formation of d-fructose-6-phosphate from d-xylose, as opposed to the accumulation of d-fructose-1,6-bisphosphate that is normally observed when PGI1 deletants are incubated on d-fructose. This may indicate a role of PFK27 in d-xylose sensing and utilization. Overall, the sensing response was different for the PGI1 deletants, and responses to sugars that enter the glycolysis upstream of Pgi1p (d-glucose and d-galactose) were more affected than the response to those entering downstream of the reaction (d-fructose and d-xylose). Furthermore, the simultaneous exposure to sugars that entered upstream and downstream of Pgi1p (d-glucose with d-fructose, or d-glucose with d-xylose) resulted in apparent synergetic activation and deactivation of the Snf3p/Rgt2p and cAMP/PKA pathways, respectively.

Conclusions

Overall, the sensing assays indicated that the previously observed d-xylose response stems from the formation of downstream metabolic intermediates. Furthermore, our results indicate that the metabolic node around Pgi1p and the level of d-fructose-6-phosphate could represent attractive engineering targets for improved d-xylose utilization.
Exosomal circular RNA: a signature for lung cancer progression
Authors: Hussen Bashdar Mahmud , Abdullah Snur Rasool , Hama Faraj Goran Sedeeq , Rasul Mohammed Fatih , Salihi Abbas , Ghafouri-Fard Soudeh , Taheri Mohammad , Mokhtari Majid
Published: December 2022

Membrane vesicles having a diameter of 30–150 nm are known as exosomes. Several cancer types secrete exosomes, which may contain proteins, circular RNAs (circRNAs), microRNAs, or DNA. CircRNAs are endogenous RNAs that do not code for proteins and can create continuous and covalently closed loops. In cancer pathogenesis, especially metastasis, exosomal circRNAs (exo-circRNAs) have a crucial role mainly due to the frequently aberrant expression levels within tumors. However, neither the activities nor the regulatory mechanisms of exo-circRNAs in advancing lung cancer (LC) are obvious. A better understanding of the regulation and network connections of exo-circRNAs will lead to better treatment for LCs. The main objective of the current review is to highlight the functions and mechanisms of exo-circRNAs in LC and assess the relationships between exo-circRNA dysregulation and LC progression. In addition, underline the possible therapeutic targets based on exo-circRNA modulating.
NRP1 inhibition modulates radiosensitivity of medulloblastoma by targeting cancer stem cells
Authors: Douyère Manon , Gong Caifeng , Richard Mylène , Pellegrini-Moïse Nadia , Daouk Joël , Pierson Julien , Chastagner Pascal , Boura Cédric
Published: December 2022

Background

Medulloblastoma (MB) is the most common pediatric malignant brain tumor. Despite current therapies, the morbidity and recurrent risk remains significant. Neuropilin-1 receptor (NRP1) has been implicated in the tumor progression of MB. Our recent study showed that NRP1 inhibition stimulated MB stem cells differentiation. Consequently, we hypothesized that targeting NRP1 in medulloblastoma could improve current treatments.

Methods

NRP1 inhibition with a novel peptidomimetic agent, MR438, was evaluated with radiotherapy (RT) in MB models (DAOY, D283-Med and D341-Med) in vitro on cancer stem-like cells as well as in vivo on heterotopic and orthotopic xenografts.

Results

We show that NRP1 inhibition by MR438 radiosensitizes MB stem-like cells in vitro. In heterotopic DAOY models, MR438 improves RT efficacy as measured by tumor growth and mouse survival. In addition, clonogenic assays after tumor dissociation showed a significant reduction in cancer stem cells with the combination treatment. In the same way, a benefit of the combined therapy was observed in the orthotopic model only for a low cumulative irradiation dose of 10 Gy but not for 20 Gy.

Conclusions

Finally, our results demonstrated that targeting NRP1 with MR438 could be a potential new strategy and could limit MB progression by decreasing the stem cell number while reducing the radiation dose.
Performance of antigen detection for HRP2-based malaria rapid diagnostic tests in community surveys: Tanzania, July–November 2017
Authors: Rogier Eric , Bakari Catherine , Mandara Celine I. , Chiduo Mercy G. , Plucinski Mateusz , Nace Douglas , Battle Nastassia , Chacky Franky , Rumisha Susan F. , Molteni Fabrizio , Mandike Renata , Mkude Sigsbert , Njau Ritha , Mohamed Ally , Udhayakumar Venkatachalam , Ishengoma Deus S.
Published: December 2022

Background

Malaria rapid diagnostic tests (RDTs) based on the detection of the Plasmodium falciparum histidine-rich protein 2 (HRP2) antigen are widely used for detection of active infection with this parasite and are the only practical malaria diagnostic test in some endemic settings. External validation of RDT results from field surveys can confirm appropriate RDT performance.

Methods

A community-based cross-sectional survey was conducted between July and November 2017 enrolling participants of all ages in households from 15 villages in four border regions of Tanzania: Geita, Kigoma, Mtwara and Ruvuma. All participants had an RDT performed in the field and provided a blood sample for later laboratory multiplex antigen detection of HRP2. In assessing the continuous HRP2 levels in participant blood versus RDT result, dose–response logistic regression provided quantitative estimates for HRP2 limit of detection (LOD).

Results

From the 15 study villages, 6941 persons were enrolled that had a RDT at time of enrollment and provided a DBS for later laboratory antigen detection. RDT positive prevalence for the HRP2 band by village ranged from 20.0 to 43.6%, but the magnitude of this prevalence did not have an effect on the estimated LOD of RDTs utilized in different villages. Overall, HRP2 single-target tests had a lower LOD at the 95% probability of positive RDT (4.3 ng/mL; 95% CI 3.4–5.4) when compared to pLDH/HRP2 dual target tests (5.4 ng/mL; 4.5–6.3), though this difference was not significant. With the exception of one village, all other 14 villages (93.3%) showed RDT LOD estimates at 90% probability of positive RDT between 0.5 and 12.0 ng/mL.

Conclusions

Both HRP2-only and pLDH/HRP2 combo RDTs utilized in a 2017 Tanzania cross-sectional survey of border regions generally performed well, and reliably detected HRP2 antigen in the low ng/mL range. Though single target tests had lower levels of HRP2 detection, both tests were within similar ranges among the 15 villages. Comparison of quantitative HRP2 detection limits among study sites can help interpret RDT testing results when generating population prevalence estimates for malaria infection.
Pro-efferocytic macrophage membrane biomimetic nanoparticles for the synergistic treatment of atherosclerosis via competition effect
Authors: Sha Xuan , Dai Yue , Chong Lijuan , Wei Min , Xing Mengyuan , Zhang Chun , Li Jingjing
Published: December 2022

Macrophages participate in many links in the pathological process of atherosclerosis (AS) and the regulation of influence of macrophages at the molecular level might be a new avenue for AS treatment. For this aim, the macrophage membrane biomimetic nanoparticles, derived from macrophage membrane coated SHP1i-loaded liposome NPs (MM@Lips-SHP1i) was designed. Due to the reservation of intrinsic membrane proteins and function from macrophages, the biomimic nanoparticles could effectively evade clearance by the immune system, prolong blood circulation time and actively tend and aggregate to atherosclerotic plaques. More importantly, in the plaque area, MM@Lips-SHP1i nanoparticles could compete with macrophages in vivo to bind with oxidized low-density lipoprotein (oxLDL) and lipopolysaccharide (LPS), reduce uptake of new lipids by macrophages, reduce foam cell formation, and inhibit the expression of pro-inflammatory cytokines. In addition, small molecule inhibitor of SHP-1, the downstream effector molecule of CD47 loaded in macrophage membrane biomimetic nanoparticles could interrupt CD47-SIRPα signal transduction in monocytes and macrophages, thereby enhancing the efferocytosis of macrophages, inhibiting the progression of plaque, achieving synergistic treatment of atherosclerosis. This work focuses on the key process in the formation of AS, macrophage foaming and chronic inflammation, and is based on the fact that macrophage membrane biomimetic nanoparticles can preserve the key surface proteins of macrophages closely related to the formation of AS, providing a new avenue to inhibit the progression of AS by utilizing the biological characteristics of macrophage membrane in macrophage membrane biomimetic nanoparticles.
Assessing feasibility, construct validity, and reliability of a new aged care-specific preference-based quality of life instrument: evidence from older Australians in residential aged care
Authors: Khadka J , Hutchinson C , Milte R , Cleland J , Muller A , Bowes N , Ratcliffe J
Published: December 2022

Background

Quality of Life-Aged Care Consumers (QOL-ACC) is a new older-person-specific quality of life instrument designed for application in quality assessment and economic evaluation in aged care. The QOL-ACC was designed from its inception with older people receiving aged care services ensuring its strong content validity. Given that the QOL-ACC has already been validated in home care settings and a preference-weighted value set developed, we aimed to assess feasibility, construct validity and reliability of the QOL-ACC in residential aged care settings. 

Methods

Individuals living in residential aged care facilities participated in an interviewer-facilitated survey. The survey included the QOL-ACC, QCE-ACC (quality of aged care experience measure) and two other preference-based quality of life instruments (ASCOT and EQ-5D-5L). Feasibility was assessed using missing data and ceiling/floor effects. Construct validity was assessed by exploring the relationship between the QOL-ACC and other instruments (convergent validity) and the QOL-ACC’s ability to discriminate varying levels of self-rated health and quality of life. Internal consistency reliability was assessed using Cronbach’s alpha (α).

Results

Of the 200 residents (mean age, 85 ± 7.7 years) who completed the survey, 60% were female and 69% were born in Australia. One in three participating residents self-rated their health as fair/poor. The QOL-ACC had no missing data but had small floor effects (0.5%) and acceptable ceiling effects (7.5%). It demonstrated moderate correlation with ASCOT (r = 0.51, p < 0.001) and EQ-5D-5L (r = 0.52, p < 0.001) and a stronger correlation with the QCE-ACC (r = 0.57, p < 0.001). Residents with poor self-rated health and quality of life had significantly lower scores on the QOL-ACC. The internal consistency reliability of the QOL-ACC and its dimensions was good (α = 0.70–0.77).

Conclusions

The QOL-ACC demonstrated good feasibility, construct validity and internal consistency reliability to assess aged care-related quality of life. Moderate correlations of the QOL-ACC and other instruments provide evidence of its construct validity and signifies that the QOL-ACC adds non-redundant and non-interchangeable information beyond the existing instruments. A stronger correlation with the QCE-ACC than other instruments may indicate that quality of life is more intimately connected with the care experience than either health- or social-related quality of life in residential aged care settings.
Identifying hepatocellular carcinoma patients with survival benefits from surgery combined with chemotherapy: based on machine learning model
Authors: Hu Jie , Gong Ni , Li Dan , Deng Youyuan , Chen Jiawei , Luo Dingan , Zhou Wei , Xu Ke
Published: December 2022

Background

Hepatocellular carcinoma (HCC) is still fatal even after surgical resection. The purpose of this study was to analyze the prognostic factors of 5-year survival rate and to establish a model to identify HCC patients with gain of surgery combined with chemotherapy.

Methods

All patients with HCC after surgery from January 2010 to December 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate logistic analysis were used to analyze the prognostic factors of patients, and the risk prediction model of 5-year survival rate of HCC patients was established by classical decision tree method. Propensity score matching was used to eliminate the confounding factors of whether to receive chemotherapy in high-risk group or low-risk group.

Results

One-thousand six-hundred twenty-five eligible HCC patients were included in the study. Marital status, α-fetoprotein (AFP), vascular infiltration, tumor size, number of lesions, and grade were independent prognostic factors affecting the 5-year survival rate of HCC patients. The area under the curve of the 5-year survival risk prediction model constructed from the above variables was 0.76, and the classification accuracy, precision, recall, and F1 scores were 0.752, 0.83, 0.842, and 0.836, respectively. High-risk patients classified according to the prediction model had better 5-year survival rate after chemotherapy, while there was no difference in 5-year survival rate between patients receiving chemotherapy and patients not receiving chemotherapy in the low-risk group.

Conclusions

The 5-year survival risk prediction model constructed in this study provides accurate survival prediction information. The high-risk patients determined according to the prediction model may benefit from the 5-year survival rate after combined chemotherapy.
Two phenotypes of chronic recurrent multifocal osteomyelitis with different patterns of bone involvement
Authors: Cebecauerová Dita , Malcová Hana , Koukolská Veronika , Kvíčalová Zuzana , Souček Ondřej , Wagenknecht Lukáš , Bronský Jiří , Šumník Zdeněk , Kynčl Martin , Cebecauer Marek , Horváth Rudolf
Published: December 2022

Introduction

Chronic Recurrent Multifocal Osteomyelitis (CRMO) is an autoinflammatory bone disorder with predominantly paediatric onset. Children present with multifocal osteolytic lesions accompanied by bone pain and soft tissue swelling. Patients often exhibit extraosseous co-morbidities such as psoriasis, inflammatory bowel disease, and arthritis.

Objectives

Comparison of children with two different phenotypes of CRMO defined by presence or absence of extraosseous co-morbidities.

Methods

Children diagnosed with CRMO at the Motol University Hospital between 2010 and 2020 were retrospectively reviewed, and according to the absence or presence of extraosseous manifestations divided into two cohorts – bone limited CRMO and complex CRMO. The two groups were compared in terms of demographic data, age at disease onset, number and site of bone lesions, laboratory biomarker values, and need of escalation to a second-line therapy.

Results

Thirty-seven children (30 female, 7 male) with confirmed CRMO were included in the analysis. The mean age at disease onset was 10 years. All but 3 patients presented with multifocal disease. Twenty-three children (62%) had at least one extraosseous manifestation (13 sacroiliitis, 8 inflammatory bowel disease, 6 skin disease [acne, pustulosis, or psoriasis], 7 arthritis). Complex CRMO was associated with a significantly higher ESR rate (p = 0.0064) and CRP level (p = 0.018). The groups did not differ in number of foci or in age at disease onset. Bone lesion distribution differed between the two groups with significantly more frequent involvement of clavicle (p = 0.011) and pelvis (p = 0.038) in patients with complex CRMO. Children with complex CRMO more often needed escalation of therapy to DMARDs and biologic agents.

Conclusion

Our data suggest that CRMO affecting solely the skeleton has milder course compared to complex CRMO with extraskeletal features. Further studies are needed to explore the clinical as well as the patient reported outcomes and promote individually tailored therapeutic strategies in both CRMO phenotypes.
Effect of ovarian growth factors on ultra-structural maturation in frozen human immature oocytes after in vitro maturation: a comparative study
Authors: Akbari Hakimeh , Mohammadi Masoud
Published: December 2022

Background

In artificial reproductive technique (ART), nearly 20% of human oocytes are immature in the germinal vesicle (GV) phase. Consequently, the best method for reserving them is cryopreserving GV oocytes, and in vitro maturation (IVM) is recommended. The aim of this study was to determine the ultrastructure characteristics of fresh and vitrified immature human oocytes after in vitro maturation in conditioned mediums.

Methods

This study was a comparative laboratory study carried out in 2018 at Afzalipur Infertility Center in Kerman. 170 fresh and 198 vitrified GV oocytes were cultured within three IVM mediums; α-mem as control medium, α-mem supplemented with human bone marrow mesenchymal stem cells (BM-MSCs) and α-mem supplemented with ovarian growth factors (O.F). After 48 h, the maturation rate and morphological feature of IVM oocytes [132 fresh IVM (fIVM) and 134 vitrified IVM (vIVM)] were evaluated. For the ultrastructure study, 10 IVM oocytes from each medium were compared with 10 fresh in vivo oocytes cancelled from ART.

Results

The survival rate of vitrified GV oocyte after thawing was 88.88%. The oocyte maturation rate was reduced in vIVM compared to the fIVM group (76.33% vs. 77.95%); the highest oocyte maturation rate in the O.F fIVM and lowest in α-mem vIVM (82.35% vs. 71.42%). The lowest number of cortical granules was observed in α-mem vIVM, but the greatest presence of M-SER aggregates was in O.F fIVM. In vIVM oocytes, the oolemma contained irregular little microvillus organization.

Conclusions

The O.F mediums have shown the highest maturation which defends the oocyte ultra-structural conservation.
Factors associated with HIV self-testing among female university students in Uganda: a cross-sectional study
Authors: Segawa Ivan , Bakeera-Kitaka Sabrina , Ssebambulidde Kenneth , Muwonge Timothy R. , Oriokot Lorraine , Ojiambo Kevin Ouma , Mujugira Andrew
Published: December 2022

Background

Adolescent girls and young women (AGYW) at institutions of higher learning are at high risk of HIV, and conventional HIV testing services may not reach them sufficiently. HIV self-testing (HIVST) scalability can be informed by identifying AGYW who have used or are interested in using HIVST. We aimed to determine factors associated with use and willingness to use HIVST among female university students.

Methods

An online cross-sectional survey was conducted among 483 female students at Makerere University, Uganda. Proportions of students who have used or are willing to use HIVST and their associated factors were determined. Modified Poisson regression models were used to estimate prevalence ratios (PR) and their 95% confidence intervals (CI).

Results

The median age of the participants was 22 (Interquartile range [IQR] 21–23) years, and 21% had never tested for HIV. Over 93% were willing to utilize HIVST, and 19% had ever used HIV self-test kits. Increasing age (adjusted prevalence ratio [aPR] 1.23 per year, 95% CI 1.07–1.43) was significantly associated with HIVST use. Predictors of willingness to self-test for HIV were college type (arts vs. science-based, aPR 0.92, 95% CI 0.88–0.97), number of sexual partners (one, aPR 1.07, 95% CI 1.03–1.12 or ≥ 2, aPR 1.08, 95% CI 1.04–1.19, vs. none), alcohol (aPR 1.04, 95% CI: 1.00–1.09) or injection drug (aPR 1.04, 95% CI 1.00–1.09) use, a history of sexually transmitted infections in past 12 months (aPR 1.05, 95% CI 1.01–1.09), and HIV testing experience (tested in past 12 months, aPR 1.12, 95% CI 1.02–1.22 or over 12 months, aPR 1.13, 95% CI 1.03–1.24, vs. never tested).

Conclusion

HIVST was highly acceptable despite its limited use. This study demonstrates female student characteristics that can be leveraged to scale up HIVST programs in higher institutions of learning.
Drug synergy discovery of tavaborole and aminoglycosides against Escherichia coli using high throughput screening
Authors: Liu Shasha , She Pengfei , Li Zehao , Li Yimin , Li Linhui , Yang Yifan , Zhou Linying , Wu Yong
Published: December 2022

High incidences of urinary tract infection (UTI) of aminoglycosides-resistant E.coli causes a severe burden for public health. A new therapeutic strategy to ease this crisis is to repurpose non-antibacterial compounds to increase aminoglycosides sensibility against multidrug resistant E.coli pathogens. Based on high throughput screening technology, we profile the antimicrobial activity of tavaborole, a first antifungal benzoxaborole drug for onychomycosis treatment, and investigate the synergistic interaction between tavaborole and aminoglycosides, especially tobramycin and amikacin. Most importantly, by resistance accumulation assay, we found that, tavaborole not only slowed resistance occurrence of aminoglycosides, but also reduced invasiveness of E.coli in combination with tobramycin. Mechanistic studies preliminary explored that tavaborole and aminoglycosides lead to mistranslation, but would be still necessary to investigate more details for further research. In addition, tavaborole exhibited low systematic toxicity in vitro and in vivo, and enhanced aminoglycoside bactericidal activity in mice peritonitis model. Collectively, these results suggest the potential of tavaborole as a novel aminoglycosides adjuvant to tackle the clinically relevant drug resistant E. coli and encourages us to discover more benzoxaborole analogues for circumvention of recalcitrant infections.
Proteomic signatures of schizophrenia-sourced iPSC-derived neural cells and brain organoids are similar to patients' postmortem brains
Authors: Nascimento Juliana Minardi , Saia-Cereda Verônica M. , Zuccoli Giuliana S. , Reis-de-Oliveira Guilherme , Carregari Victor Corasolla , Smith Bradley J. , Rehen Stevens K. , Martins-de-Souza Daniel
Published: December 2022

Background

Schizophrenia is a complex and severe neuropsychiatric disorder, with a wide range of debilitating symptoms. Several aspects of its multifactorial complexity are still unknown, and some are accepted to be an early developmental deficiency with a more specifically neurodevelopmental origin. Understanding the timepoints of disturbances during neural cell differentiation processes could lead to an insight into the development of the disorder. In this context, human brain organoids and neural cells differentiated from patient-derived induced pluripotent stem cells are of great interest as a model to study the developmental origins of the disease.

Results

Here we evaluated the differential expression of proteins of schizophrenia patient-derived neural progenitors (NPCs), early neurons, and brain organoids in comparison to healthy individuals. Using bottom-up shotgun proteomics with a label-free approach for quantitative analysis, we found multiple dysregulated proteins since NPCs, modified, and disrupted the 21DIV neuronal differentiation, and cerebral organoids. Our experimental methods have shown impairments in pathways never before found in patient-derived induced pluripotent stem cells studies, such as spliceosomes and amino acid metabolism; but also, those such as axonal guidance and synaptogenesis, in line with postmortem tissue studies of schizophrenia patients.

Conclusion

In conclusion, here we provide comprehensive, large-scale, protein-level data of different neural cell models that may uncover early events in brain development, underlying several of the mechanisms within the origins of schizophrenia.
Solving nonlinear and dynamic programming equations on extended b-metric spaces with the fixed-point technique
Authors: Belhenniche Abdelkader , Guran Liliana , Benahmed Sfya , Lobo Pereira Fernando
Published: December 2022

In this article, we present an approach to solve a wide range of nonlinear equations formulated in extended b-metric spaces based on a new fixed-point theorem on these spaces. This research effort was motivated by challenges arising in solving pattern problems efficiently that can not be addressed by using standard metric spaces. Our approach relies on a novel common fixed-point theorem for Ćirić-type operators on extended b-metric spaces requiring only very weak assumptions that we present and derive in this article. The proposed approach is illustrated by applications asserting the existence and uniqueness of the solutions to Bellman equations, Volterra integral equations, and fractional differential equations formulated in extended b-metric spaces. Moreover, the obtained results provide general constructive recursive procedures to solve the above types of nonlinear equations.