bluuebunny/crossref_metadata_2025 huggingface dataset:
Multimodal Approach for Pediatric Mandibular Fractures: A Case Series
Authors: Gehlot Neelima , Gupta D. S. , Pillai Sooraj S. , Singh Snigdha
Published: September 2023

Background

The management of facial fractures varies due to a variety of reasons in the pediatric age groups. The clinicians should therefore attune themselves to managing pediatric patients and the variations thereof. Every modality mentioned in the literature has its own advantages and disadvantages. The right choice of treatment by clinicians depends on their knowledge of pediatric anatomy, physiology, age-dependent bone growth, and the type and extent of fractures. Three different modalities of treatment in the form of circummandibular wiring, intermaxillary fixation and open reduction, with internal fixation were rendered to the patients, considering various factors such as the patient’s age, location of the fracture line, status of occlusion, and dentition. All three modalities showed good results in the form of adequate reduction and no post-op complications.

Conclusion

Pediatric trauma is a challenging entity for the surgeon. The choice of the ideal treatment modality ultimately depends on the presence of tooth buds and the maintenance of uninterrupted growth of the jaw bone. Thus, a well-thought-out and customized treatment plan should be devised for each individual case.
Oxidative stress as a key modulator of cell fate decision in osteoarthritis and osteoporosis: a narrative review
Authors: Riegger Jana , Schoppa Astrid , Ruths Leonie , Haffner-Luntzer Melanie , Ignatius Anita
Published: September 2023

During aging and after traumatic injuries, cartilage and bone cells are exposed to various pathophysiologic mediators, including reactive oxygen species (ROS), damage-associated molecular patterns, and proinflammatory cytokines. This detrimental environment triggers cellular stress and subsequent dysfunction, which not only contributes to the development of associated diseases, that is, osteoporosis and osteoarthritis, but also impairs regenerative processes. To counter ROS-mediated stress and reduce the overall tissue damage, cells possess diverse defense mechanisms. However, cellular antioxidative capacities are limited and thus ROS accumulation can lead to aberrant cell fate decisions, which have adverse effects on cartilage and bone homeostasis. In this narrative review, we address oxidative stress as a major driver of pathophysiologic processes in cartilage and bone, including senescence, misdirected differentiation, cell death, mitochondrial dysfunction, and impaired mitophagy by illustrating the consequences on tissue homeostasis and regeneration. Moreover, we elaborate cellular defense mechanisms, with a particular focus on oxidative stress response and mitophagy, and briefly discuss respective therapeutic strategies to improve cell and tissue protection.
A survey on Helicobacter pylori infection rate in Hainan Province and analysis of related risk factors
Authors: Chen Run-xiang , Zhang Da-ya , Zhang Xiaodong , Chen Shiju , Huang Shimei , Chen Chen , Li Da , Zeng Fan , Chen Jiajia , Mo Cuiyi , Gao Lei , Zeng Juntao , Xiong Jianxin , Chen Zhai , Bai Feihu
Published: September 2023

Objective

The aim of this study was to understand the prevalence and potential risk factors of Helicobacter pylori (H. pylori) infection in Hainan Province, China.

Methods

We conducted this study in 21 health service stations in 5 cities of Hainan Province from August 2022 to April 2023. We selected the various participants based on a stratified whole-group sampling method. The 14C-UBT was used to analyze H. pylori infection in 3632 participants. We also analyzed the possible relationship between variables and H. pylori infection based on chi-square test and multifactorial logistic regression. The model was evaluated by performing a Hosmer–Lemeshow goodness-of-fit test and plotting receiver operating characteristic(ROC) curves.

Results

In total, the results of 3632 eligible participants (age: 14 to 93 years) were included in the analysis. The total prevalence of H. pylori infection in Hainan Province was approximately 38.7%. The prevalence of H. pylori infection was found to increase with age, stabilized in the age group of 45 to 64 years, but peaked in the age group of 65 years and older. In multifactorial analysis, the prevalence of H. pylori infection was positively associated with middle-aged adults (45–64 years), older adults (≥ 65 years), drinking, farmers, natural labor, routinely share utensils, have habit of frequent betel nut consumption, upper gastrointestinal symptoms, and family history of gastric cancer. The factors negatively associated with prevalence included family size ≤ 3, washing hands often before meals, frequent exercise, regular meals, and frequent consumption of fruits and vegetables. In addition, the Hosmer–Lemeshow test showed a good fit (χ2 = 12.983, P = 0.112) and the area under ROC was 0.631 (95%CI: 0.613 ~ 0.649).

Conclusion

The prevalence of H. pylori infection in Hainan Province was observed to be moderate and closely related to age, local socioeconomic conditions, hygienic status and dietary habits.
The prevalence of elder abuse and risk factors: a cross-sectional study of community older adults
Authors: Nemati-Vakilabad Reza , Khalili Zahra , Ghanbari-Afra Leila , Mirzaei Alireza
Published: September 2023

Background

The old people population is increasing worldwide. Along with their increasing population, an increase in elder abuse cases is predicted. Elder abuse is a neglected problem, and many cases go unreported. This study was conducted to identify types of elder abuse and examine associated risk factors.

Methods

This cross-sectional analytical study was conducted on 500 older people in Ardabil (northwestern Iran). Data was collected over three months, from June to September 2020. Data was collected using a demographic information form and the Domestic Elder Abuse questionnaire. The data were analyzed using SPSS software (version 22). Logistic regression was used to identify factors related to elder abuse.

Results

The results showed that out of the 500 participants, 258 (51.6%) were male, and 242 (48.2%) were female. Among the 500 participants, 377 individuals (75/4%) reported experiencing at least one type of abuse in the past year. The highest rate of elder abuse was observed for emotional neglect (47.2%) and psychological abuse (40.8%), while the lowest rate was measured for rejection (15.4%) and physical abuse (12.4%). The results indicated that elder abuse was significantly associated with chronic illness (OR = 0.601, 95% CI: 0.391–0.922) and having 1–4 children (OR = 1.275, 95% CI: 1.137–1.430).

Conclusion

Considering the high level of elder abuse and its dangerous effects on the quality of life for older people, it is essential to develop appropriate programs to increase awareness among older people and their families.
Quality of life and well-being during the COVID-19 pandemic: associations with loneliness and social isolation in a cross-sectional, online survey of 2,207 community-dwelling older Canadians
Authors: Briere Jennifer , Wang Sophia Haotong , Khanam Ulfat Ara , Lawson Josh , Goodridge Donna
Published: September 2023

Background

The far-reaching health and social sequelae of the COVID-19 pandemic among older adults have the potential to negatively impact both quality of life (QoL) and well-being, in part because of increased risks of loneliness and social isolation. The aim of this study was to examine predictors of QoL and well-being among Canadian older adults within the context of the pandemic, including loneliness and social isolation.

Methods

This cross-sectional, online survey recruited older adult participants through community organizations and research participant panels. Measures included the: Older People’s Quality of Life Scale-B, WHO-5, DeJong Gierveld Loneliness Scale, Lubben Social Network Scale and five COVID-19 specific items assessing impact on loneliness and social isolation. Multiple linear regression models were used to adjust for potential confounders.

Results

A total of 2,207 older Canadians (55.7% female, with a mean age of 69.4 years) responded to the survey. Over one-third strongly disagreed that the pandemic had had a significant effect on either their mental (35.0%) or physical health (37.6%). Different patterns of predictors were apparent for QoL and well-being. After adjusting for all variables in the models, the ability of income to meet needs emerged as the strongest predictor of higher QoL, but was not associated with well-being, except for those who chose not to disclose their income adequacy. Age was not associated with either QoL or well-being. Females were more likely to experience lower well-being (β=-2.0, 95% C.I. =-4.0,-0.03), but not QoL. Reporting three or more chronic health conditions and that the COVID-19 pandemic had a negative impact on mental health was associated with lower QoL and well-being. Loneliness was a predictor of reduced QoL (β=-1.4, 95% C.I. =--1.6, -1.2) and poor well-being (β=-3.7, 95% C.I. =-4.3,-3.0). A weak association was noted between QoL and social isolation.

Conclusions

The COVID-19 pandemic is associated with differential effects among older adults. In particular, those with limited financial resources and those with multiple chronic conditions may be at more risk to suffer adverse QoL and well-being consequences. Loneliness may be a modifiable risk factor for decreased QoL and well-being amenable to targeted interventions.
Meningitis caused by oral anaerobes detected using mNGS tool: a case report and review of literature
Authors: Zhong Xiaoqing , Wang Miaomiao , Meng Qingxia , Jiang Xuebin , Guo Zhendong , Zhang Yunzhou , Gao Daiquan
Published: September 2023

Background

Bacterial meningitis is a central nervous system (CNS) infection disease of the meninges and brain parenchyma caused by the bacteria. Few cases of meningitis related to oral anaerobes have been reported in the literature. Here, we report a case of meningitis in a middle-aged woman, caused by oral anaerobes.

Case presentation

A 58-year-old woman was admitted to hospital with fever, headache for 21 days and left limb weakness for 2 days. The blood cell counts (11.73 × 109/L), neutrophil counts (9.22 × 109/L) and high-sensitivity C-reactive protein levels (> 5.00 mg/L) were elevated. The brain computerized tomography (CT) scanning indicated the new right thalamus infarct. The brain cranial-enhanced magnetic resonance imaging (MRI) showed the right lateral paraventricular and right thalamic infarct, and abnormal signal in occipital horns of bilateral lateral ventricles were increased. In addition, the brain enhanced nuclear magnetic resonance (NMR) scanning suggested that meninges were thickened and enhanced at the base of the brain, with meningitis changes. The neck CT angiography (CTA) revealed arteriosclerotic changes. The metagenomic next-generation sequencing (mNGS) revealed Eubacterium brachy, Porphyromonas gingivalis, Fusobacterium nucleatum and Torque teno virus in her cerebrospinal fluid (CSF). The patient was diagnosed with purulent meningitis caused by infection of oral anaerobes, and treated with mannitol, ceftriaxone and vancomycin. Her symptoms alleviated. Subsequently, she was transferred to the infectious department and treated with ceftriaxone plus metronidazole (anti-anaerobes) and mannitol (reduce intracranial pressure). Her symptoms improved and currently received rehabilitation treatment.

Conclusion

We herein report a rare case involving meningitis caused by infection of oral anaerobes. The mNGS can accurately detect the pathogens of infectious diseases.
A combined clinical and specific genes’ model to predict live birth for in vitro fertilization and embryo transfer patients
Authors: Meng Shihui , Shi Cheng , Jia Yingying , Fu Min , Zhang Tianzhen , Wu Na , Han Hongjing , Shen Huan
Published: September 2023

Background

We aimed to develop an accurate model to predict live birth for patients receiving in vitro fertilization and embryo transfer (IVF-ET) treatment.

Methods

This is a prospective nested case–control study. Women aged between 18 and 38 years, whose body mass index (BMI) were between the range of 18.5–24 kg/m2, who had an endometrium of ≥ 8 mm at the thickest were enrolled from 2018/9 to 2020/8. All patients received IVF-ET treatment and were followed up until Jan. 2022 when they had reproductive outcomes. Endometrial samples during the window of implantation (LH + 6 to 9 days) were subjected to analyze specific endometrial receptivity genes’ expression using real-time PCR (RT-PCR). Patients were divided into live birth group and non-live birth group based on IVF-ET outcomes. Clinical signatures relevant to live birth were collected, analyzed, and used to establish a predictive model for live birth by univariate analysis (clinical model). Specific endometrial receptivity genes’ expression was analyzed, selected, and used to construct a predictive model for live birth by The Least Absolute Shrinkage and Selection Operator (LASSO) analysis (gene model). Finally, significant clinical factors and genes were used to construct a combined model for predicting live birth using multivariate logistical regression (combined model). Different models’ Area Under Curve (AUC) were compared to identify the most predictive model.

Results

Thirty-nine patients were enrolled in the study, twenty-four patients had live births, fifteen did not. In univariate analysis, the odds of live birth for women with ovulation dysfunction was 4 times higher than that for women with other IVF-ET indications (OR = 4.0, 95% CI: 1.125 − 8.910, P = 0.018). Age, body mass index, duration of infertility, primary infertility, repeated implantation failure, antral follicle counting, ovarian sensitivity index, anti-Mullerian hormone, controlled ovarian hyperstimulation protocol and duration, total dose of FSH/hMG, number of oocytes retrieved, regiment of endometrial preparation, endometrium thickness before embryo transfer, type of embryo transferred were not associated with live birth (P > 0.05). Only ovulation dysfunction was used to construct the clinical model and its AUC was 0.688. In lasso analysis, GAST, GPX3, THBS2 were found to promote the risk of live birth. AUCs for GAST, GPX3, THBS2 reached to 0.736, 0.672, and 0.678, respectively. The gene model was established based on these three genes and its AUC was 0.772. Ovulation dysfunction, GAST, GPX3, and THBS2 were finally used to construct the combined model, reaching the highest AUC (AUC = 0.842).

Conclusions

Compared to the single model, the combined model of clinical (Ovulation dysfunction) and specific genes (GAST, GPX3, THBS2) was more accurate to predict live birth for IVF-ET patients.
A randomized phase II trial of MR-guided prostate stereotactic body radiotherapy administered in 5 or 2 fractions for localized prostate cancer (FORT)
Authors: Wolfe Sydney , Diven Marshall A. , Marciscano Ariel E. , Zhou Xi Kathy , Kishan A. U. , Steinberg M. L. , Miccio Joseph A. , Camilleri Philip , Nagar Himanshu
Published: September 2023

Background

Ultra-hypofractionated regimens for definitive prostate cancer (PCa) radiotherapy are increasingly utilized due in part to promising safety and efficacy data complemented by greater patient convenience from a treatment course requiring fewer sessions. As such, stereotactic body radiation therapy (SBRT) is rapidly emerging as a standard definitive treatment option for patients with localized PCa. The commercially available magnetic resonance linear accelerator (MR-LINAC) integrates MR imaging with radiation delivery, providing several theoretical advantages compared to computed tomography (CT)-guided radiotherapy. MR-LINAC technology facilitates improved visualization of the prostate, real-time intrafraction tracking of prostate and organs-at-risk (OAR), and online adaptive planning to account for target movement and anatomical changes. These features enable reduced treatment volume margins and improved sparing of surrounding OAR. The theoretical advantages of MR-guided radiotherapy (MRgRT) have recently been shown to significantly reduce rates of acute grade ≥ 2 GU toxicities as reported in the prospective randomized phase III MIRAGE trial, which compared MR-LINAC vs CT-based 5 fraction SBRT in patients with localized PCa (Kishan et al. JAMA Oncol 9:365-373, 2023). Thus, MR-LINAC SBRT–utilizing potentially fewer treatments–is warranted and clinically relevant for men with low or intermediate risk PCa electing for radiotherapy as definitive treatment.

Methods/Design

A total of 136 men with treatment naïve low or intermediate risk PCa will be randomized in a 1:1 ratio to 5 or 2 fractions of MR-guided SBRT using permuted block randomization. Randomization is stratified by baseline Expanded PCa Index Composite (EPIC) bowel and urinary domain scores. Patients undergoing 5 fractions will receive 37.5 Gy to the prostate over 10–14 days and patients undergoing 2 fractions will receive 25 Gy to the prostate over 7–10 days. The co-primary endpoints are GI and GU toxicities as measured by change scores in the bowel and urinary EPIC domains, respectively. The change scores will be calculated as pre-treatment (baseline) score subtracted from the 2-year score.

Discussion

FORT is an international, multi-institutional prospective randomized phase II trial evaluating whether MR-guided SBRT delivered in 2 fractions versus 5 fractions is non-inferior from a gastrointestinal (GI) and genitourinary (GU) toxicity standpoint at 2 years post-treatment in men with low or intermediate risk PCa.

Trial registration

Clinicaltrials.gov identifier: NCT04984343. Date of registration: July 30, 2021.

Protocol version: 4.0, Nov 8, 2022.
The relationship between body dissatisfaction, lifestyle, and nutritional status among university students in Southern China
Authors: Hao Ming , Yang Juan , Xu Shiliang , Yan Wenjing , Yu Hongfei , Wang Qi
Published: September 2023

Background

In recent years, obesity in early adulthood has become an urgent global public health concern. Body dissatisfaction may have adverse effects on lifestyle habits, leading to obesity. However, research on nutritional status and body dissatisfaction among Chinese young adults is still insufficient. Therefore, this study aimed to analyze the relationship between body dissatisfaction, dietary habits, physical activity, and nutritional status among university students. In addition, we explored the feasibility of improving university students’ nutritional status by improving the levels of body dissatisfaction.

Methods

This study was conducted in Ganzhou City, Jiangxi Province, China, at a randomly selected university. All 1900 undergraduate students volunteered to participate and signed the consent form. Students were required to completed anthropometric measurements and three questionnaires, which included the Physical Activity Rating Scale-3 (PARS-3), Chinese version of the Dutch Dietary Behavior Questionnaire (C-DEBQ), and Body Dissatisfaction. Of these, 1714 students (age: 18–24 years; men: 933, women: 781) with complete and valid data were included.

Results

Higher obesity levels were observed in men compared to women (p<0.01). Meanwhile, body dissatisfaction was higher in women compared to men (p<0.01). Overeating and insufficient physical activity were more problematic in women compared to in men (p<0.01). Multiple regression analyses were conducted separately, with BMI and body dissatisfaction as the dependent variables. Body dissatisfaction (β=0.72, p<0.01), muscle mass (β=0.33, p<0.01), emotional eating score (β=0.05, p<0.01), sex (β=-0.05, p<0.05) and physical activity (β=-0.04, p<0.05) score were significant predictors of obesity. Furthermore, Muscle mass (β=0.61, p<0.01), sex (β=0.54, p<0.01), restrained eating score (β=0.25, p<0.01), physical activity score (β=-0.20, p<0.01) and emotional eating score (β=0.08, p<0.01) were significant predictors of body dissatisfaction.

Conclusion

The data presented in this study highlight the impact of university students’ body dissatisfaction in China on physical activity deficiency and overeating, discovering that reducing body dissatisfaction has great potential for preventing obesity.
Overall drug treatment of idiopathic pulmonary fibrosis patients from national registries – a real-world study from Finland
Authors: Kaunisto Jaana , Salomaa Eija-Riitta , Koivisto Mari , Myllärniemi Marjukka
Published: September 2023

Background

Currently, two disease-modifying antifibrotic drugs are indicated for the treatment of idiopathic pulmonary fibrosis. The objective of this study was to analyse antifibrotic and overall prescription medication use of IPF patients in the real world.

Methods

Data was collected from the FinnishIPF registry and the Registry of the Social Insurance Institution of Finland (SII). Purchases of all prescription medicines were assessed. The frequency, the initiation interval, the duration, and the breaks of the antifibrotic treatments were defined. The association between the prescription of antifibrotic therapy and different patient-related clinical parameters was studied. Accordingly, the relationships between the delay in starting therapy and patient-related variables were analysed.

Results

Of the 263 IPF patients, 132 (50.2%) had started antifibrotic treatment during the study period 2011–2018. The mean interval from the diagnosis to the first purchase was 367 (SD 429) days. The antifibrotic drug was switched in 14% of patients. Discontinuation of therapy occurred most commonly during the first year of the treatment. The one-year persistence was 77.1% for pirfenidone and 78.9% for nintedanib. A tendency of treating patients under 75 years was noticed. Low forced vital capacity predicted earlier initiation of medication.

Conclusions

The initiation of antifibrotics after diagnosis was slow, probably due to reimbursement limitations. Younger age at diagnosis affected treatment initiation although it is unknown which patients benefit most from these medications. The reasons for discontinuation of the antifibrotic therapy during the first year should be a focus in clinical work and further studies.
Predictive factors for survival in borderline resectable and locally advanced pancreatic cancer: are these really two different entities?
Authors: de Carvalho Luís Filipe Abreu , Gryspeerdt Filip , Rashidian Niki , Van Hove Kobe , Maertens Lambertine , Ribeiro Suzane , Hoorens Anne , Berrevoet Frederik
Published: September 2023

Background

The treatment of borderline resectable (BR) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC) has evolved with a wider application of neoadjuvant chemotherapy (NACHT). The aim of this study was to identify predictive factors for survival in BR and LA PDAC.

Methods

Clinicopathologic data of patients with BR and LA PDAC who underwent surgical exploration between January 2011 and June 2021 were retrospectively collected. Survival from the date of surgery was estimated using the Kaplan-Meier method. Simple and multiple Cox proportional hazards models were fitted to identify factors associated with survival. Surgical resection was analyzed in combination with the involvement of lymph nodes as this last was only known after a formal resection.

Results

Ninety patients were surgically explored (BR: 45, LA: 45), of which 51 (57%) were resected (BR: 31, LA: 20). NACHT was administered to 43 patients with FOLFIRINOX being the most frequent regimen applied (33/43, 77%). Major complications (Clavien-Dindo grade III and IV) occurred in 7.8% of patients and 90-day mortality rate was 3.3%. The median overall survival since surgery was 16 months (95% CI 12-20) in the group which underwent surgical resection and 10 months (95% CI 7-13) in the group with an unresectable tumor (p=0.001). Cox proportional hazards models showed significantly lower mortality hazard for surgical resection compared to no surgical resection, even after adjusting for National Comprehensive Cancer Network  (NCCN) classification and administration of NACHT [surgical resection with involved lymph nodes vs no surgical resection (cHR 0.49; 95% CI 0.29-0.82; p=0.007)]. There was no significant difference in survival between patients with BR and LA disease (cHR= 1.01; 95% CI 0.63-1.62; p=0.98).

Conclusions

Surgical resection is the only predictor of survival in patients with BR and LA PDAC, regardless of their initial classification as BR or LA. Our results suggest that surgery should not be denied to patients with LA PDAC a priori. Prospective studies including patients from the moment of diagnosis are required to identify biologic and molecular markers which may allow a better selection of patients who will benefit from surgery.
Emergency and sequalae management of traumatic dental injuries: a systematic survey of clinical practice guidelines
Authors: Zaror Carlos , Seiffert Andrea , Deana Naira Figueiredo , Espinoza-Espinoza Gerardo , Atala-Acevedo Claudia , Diaz Rodrigo , Carrasco-Labra Alonso
Published: September 2023

Background

The prevalence and consequences of traumatic dental injuries (TDI) make them a public health problem. Trustworthy TDI clinical practice guidelines (CPGs) assist clinicians in determining a diagnosis and guide them to the most appropriate therapy. The aim of this systematic survey was to identify and evaluate the quality of CPGs for the diagnosis, emergency management, and follow-up of TDIs.

Materials and methods

A systematic search was carried out in MEDLINE, EMBASE, Epistemonikos, Trip database, CPG websites, and dental societies to identify documents providing recommendations for the emergency and sequelae management of TDIs. Reviewers assessed the included guidelines independently and in duplicate, using the AGREE II instrument. ANOVA or Student’s t-tests were used to determine the attributes of CPGs associated with the total score in AGREE II.

Results

Ten CPGs published between 2010 and 2020 were included, mostly from Europe (n = 6). The overall agreement between reviewers was very good (0.94; 95%CI 0.91–0.97). The mean scores (the higher the score, the better the domain assessment) per domain were as follows: Scope and purpose 78.0 ± 18.9%; stakeholder involvement 46.9 ± 29.6%; rigour of development 41.8 ± 26.7%; clarity of presentation 75.8 ± 17.6%; applicability 15.3 ± 18.8%; and editorial independence 41.7 ± 41.7%. The overall mean rate was 4 ± 1.3 out of a maximum score of 7. Two guidelines were recommended by the reviewers for use in practice and rated as high quality. CPGs developed by government organizations showed a significantly higher overall score.

Conclusions

The overall quality of CPGs on TDI was suboptimal. CPG developers should synthesize the evidence and formulate recommendations using high-quality methodologies and standards in a structured, transparent, and explicit way.
Effect of blood contamination on marginal adaptation of cold ceramic and MTA angelus: a scanning electron microscopic study
Authors: Mokhtari Fatemeh , Modaresi Jalil , Bagheri Abbas
Published: September 2023

Background

This study aimed to assess the effect of blood contamination on marginal adaptation of cold ceramic (CC) and mineral trioxide aggregate (MTA) Angelus using scanning electron microscopy (SEM).

Methods

This in vitro experimental study was conducted on 24 extracted single-rooted human teeth. After cleaning and shaping, the root canals were filled with lateral compaction technique. The apical 3 mm of the roots was cut, and cavities with 3 mm depth were created at the apex. The teeth were randomly assigned to two group (n = 12) for the application of CC and MTA Angelus as retrograde filling materials. CC and MTA Angelus were prepared by mixing the powder with blood, and applied in the cavities. After 24 h, their marginal adaptation to the canal walls was assessed by SEM. Data were statistically analyzed by t-test (alpha = 0.05).

Results

The mean marginal gap was 8.98 μm in the CC, and 16.26 μm in the MTA Angelus group; this difference was statistically significant (P < 0.001).

Conclusions

The present in vitro study revealed that following complete blood contamination of powder, CC showed significantly superior marginal adaptation than MTA Angelus as shown by SEM assessment.
Application of the herbal chemical marker ranking system (Herb MaRS) to the standardization of herbal raw materials: a case study
Authors: Kaggwa Bruhan , Anywar Godwin , Munanura Edson Ireeta , Wangalwa Raphael , Kyeyune Henry , Okella Hedmon , Kamba Fadhiru Pakoyo , Engeu Ogwang Patrick
Published: September 2023

Introduction

Phytochemical standardization of herbal materials involves establishing consistent levels of one or more active ingredients or markers. It ensures the authenticity and quality of herbal materials, extracts, and their products. This research aimed to apply the herbal chemical marker ranking system (Herb MaRS) originally proposed for quality assurance of complex herbal products to establish markers for controlling the quality of herbal raw materials.

Methods

The assessment of compounds for suitability as markers was based on the Herb MaRS, with minor modifications as follows: for more objective scoring, evidence of biological activity of the potential marker compound(s) was determined at three levels based on the number of symptoms of the disease condition a compound can treat or alleviate: (i) one symptom (1 point), two symptoms (2 points), and 3 or more symptoms (3 points). The reported concentrations of the compounds were also scored as follows: concentration not determined (0 points), concentration ≥ 5 ppm (1 point), concentration ≥ 50 ppm (2 points) and availability of analytical standards (1 point). Finally, the compounds were scored for the availability of an analytical method (1 point). The compounds were scored from 0 to 8, where 8 indicated the most suitable chemical marker.

Results

The selected markers were as follows: aromadendrine, α-terpineol, globulol, and 1,8-cineol (in Eucalyptus globulus Labill. ); aloin, aloe emodin, acemannan (in Aloe barbadensis (L.) Burm.f. ), lupeol, lupenone, betulinic acid, betulin, and catechin (in Albizia coriaria Oliv.); mangiferin, catechin, quercetin, and gallic acid (in Mangifera indica L.); polygodial (in Warburgia ugandensis Sprague); azadirachtin, nimbin, nimbidin (in Azadirachta indica A. Juss. ); and 6,8,10-gingerols, and 6-shogaol (in Zingiber officinalis Roscoe).

Conclusions

Herb MaRS can be efficiently applied to select marker compounds for quality control of herbal materials. However, for herbs whose phytochemicals have not been sufficiently researched, it is difficult to establish evidence of activity, and there are no analytical standards and/or methods; this is the case for plants exclusively used in Africa. The markers identified should be incorporated into chromatographic fingerprints, their quantitative methods developed, and evaluated for applicability at the various stages of the production chain of herbal medicines; then, they can be included in future local plant monographs. There is also a need to build local capacity to isolate marker compounds, particularly those that are not sold by current vendors.
Exploring the potential of Bacillus subtilis as cell factory for food ingredients and special chemicals
Authors: Chen Taichi , Brul Stanley , Hugenholtz Jeroen
Published: September 2023

Background

Bacillus subtilis has been established as model microorganism for fundamental research in the laboratory on protein production/secretion and sporulation and as model bacterium for controlling spoilage in the food industry. It has also been used for production of (commercial) enzymes and several secondary metabolites such as vitamins. However, this doesn’t fully reflect the potential of B. subtilis as a cell-factory. Here, various strains of B. subtilis, including food-grade, spore-deficient strains and industrially used strains, were compared for their growth and metabolic potential. Industry-relevant parameters were analyzed for all strains under various aeration regimes, under anaerobic conditions, in various nutritious and nutrient-limited cultivation media, with and without organic nitrogen sources, and with and without sugar.

Results

Practical experiments were conducted to compare industrial relevant properties like growth rates, intracellular components and extracellular metabolite profile of different B. subtilis strains. Based on growth flexibility in different media, we found that some strains like NCIB3610 and DSM1092 are adapted to inorganic or organic nitrogen source utilization, which is highly relevant when considering a biorefinery approach using various cheap and abundant waste/sidestreams. Secondly, spore-deficient strains such as 3NA, 168 S and PY79S, showed advantages in microbial protein and acetolactate pathway expression, which is associated with applications in food industry for protein supplement and diacetyl production. Lastly, WB800 and PY79S exhibited potential for fermentative production of dipicolinic acid, 2,3-butanediol and lactic acid that could serve as precursors for biopolymers.

Conclusion

This study demonstrates the broad potential for more extensive industrial use of Bacillus subtilis in the (bio-based) chemical industry for use of sidestreams, in the personal care industry, in the food industry for food additive production, and in the bio-sustainable industry for biofuel and bio-degradable plastic precursors production. In addition, selecting different B. subtilis strains for specific purposes makes full use of the diversity of this species and increases the potential of B. subtilis in its contribution to the bio-based economy.
Prediction model for hyperprogressive disease in patients with advanced solid tumors received immune-checkpoint inhibitors: a pan-cancer study
Authors: Long Yaping , Yang Wenyu , Bai Yibing , Tao Haitao , Zhang Fan , Wang Lijie , Yang Bo , Huang Di , Han Xiao , Hu Yi
Published: September 2023

Background

Hyper progressive disease (HPD) describes the phenomenon that patients can’t benefit from immunotherapy but cause rapid tumor progression. HPD is a particular phenomenon in immunotherapy but lacks prediction methods. Our study aims to screen the factors that may forecast HPD and provide a predictive model for risky stratifying.

Methods

We retrospectively reviewed advanced-stage tumor patients who received immune checkpoint inhibitors (ICI) in the General PLA Hospital. Subsequently, we calculated the tumor growth kinetics ratio (TGKr) and identified typical HPD patients. Differences analysis of clinical characteristics was performed, and a predictive binary classification model was constructed.

Results

867 patients with complete image information were screened from more than 3000 patients who received ICI between January 2015 and January 2020. Among them, 36 patients were identified as HPD for TGKr > 2. After the propensity score matched, confounding factors were limited. Survival analysis revealed that the clinical outcome of HPD patients was significantly worse than non-HPD patients. Besides, we found that Body Mass Index (BMI), anemia, lymph node metastasis in non-draining areas, pancreatic metastasis, and whether combined with anti-angiogenesis or chemotherapy therapy were closely connected with the HPD incidence. Based on these risk factors, we constructed a visualised predicted nomogram model, and the Area Under Curve (AUC) is 0.850 in the train dataset, whereas 0.812 in the test dataset.

Conclusion

We carried out a retrospective study for HPD based on real-world patients and constructed a clinically feasible and practical model for predicting HPD incidence, which could help oncologists to stratify risky patients and select treatment strategies.
EYA4 promotes breast cancer progression and metastasis through its role in replication stress avoidance
Authors: de la Peña Avalos Bárbara , Tropée Romain , Duijf Pascal H. G. , Dray Eloïse
Published: September 2023

The Eyes Absent (EYA) family of proteins is an atypical group of four dual-functioning protein phosphatases (PP), which have been linked to many vital cellular processes and organogenesis pathways. The four family members of this PP family possess transcriptional activation and phosphatase functions, with serine/threonine and tyrosine phosphatase domains. EYA4 has been associated with several human cancers, with tumor-suppressing and tumor-promoting roles. However, EYA4 is the least well-characterized member of this unique family of PP, with its biological functions and molecular mechanisms in cancer progression, particularly in breast cancer, still largely unknown. In the present study, we found that the over-expression of EYA4 in breast tissue leads to an aggressive and invasive breast cancer phenotype, while the inhibition of EYA4 reduced tumorigenic properties of breast cancer cells in vitro and in vivo. Cellular changes downstream of EYA4, including cell proliferation and migration, may explain the increased metastatic power of breast cancer cells over-expressing EYA4. Mechanistically, EYA4 prevents genome instability by inhibiting the accumulation of replication-associated DNA damage. Its depletion results in polyploidy as a consequence of endoreplication, a phenomenon that can occur in response to stress. The absence of EYA4 leads to spontaneous replication stress characterized by the activation of the ATR pathway, sensitivity to hydroxyurea, and accumulation of endogenous DNA damage as indicated by increased γH2AX levels. In addition, we show that EYA4, specifically its serine/threonine phosphatase domain, plays an important and so far, unexpected role in replication fork progression. This phosphatase activity is essential for breast cancer progression and metastasis. Taken together, our data indicate that EYA4 is a novel potential breast cancer oncogene that supports primary tumor growth and metastasis. Developing therapeutics aimed at the serine/threonine phosphatase activity of EYA4 represents a robust strategy for killing breast cancer cells, to limit metastasis and overcome chemotherapy resistance caused by endoreplication and genomic rearrangements.
Bioinspired polydopamine nanoparticles as efficient antioxidative and anti-inflammatory enhancers against UV-induced skin damage
Authors: Zhang Jia , Zhou Yuqi , Jiang Zhaoting , He Chenhui , Wang Bo , Wang Qi , Wang Zeqian , Wu Tong , Chen Xiaoqi , Deng Ziwei , Li Chunying , Jian Zhe
Published: September 2023

Excessive and prolonged ultraviolet radiation (UVR) exposure causes photodamage, photoaging, and photocarcinogenesis in human skin. Therefore, safe and effective sun protection is one of the most fundamental requirements. Living organisms tend to evolve various natural photoprotective mechanisms to avoid photodamage. Among them, melanin is the main functional component of the photoprotective system of human skin. Polydopamine (PDA) is synthesized as a mimic of natural melanin, however, its photoprotective efficiency and mechanism in protecting against skin damage and photoaging remain unclear. In this study, the novel sunscreen products based on melanin-inspired PDA nanoparticles (NPs) are rationally designed and prepared. We validate that PDA NPs sunscreen exhibits superior effects on photoprotection, which is achieved by the obstruction of epidermal hyperplasia, protection of the skin barrier, and resolution of inflammation. In addition, we find that PDA NPs are efficiently intake by keratinocytes, exhibiting robust ROS scavenging and DNA protection ability with minimal cytotoxicity. Intriguingly, PDA sunscreen has an influence on maintaining homeostasis of the dermis, displaying an anti-photoaging property. Taken together, the biocompatibility and full photoprotective properties of PDA sunscreen display superior performance to those of commercial sunscreen. This work provides new insights into the development of a melanin-mimicking material for sunscreens.
Bone-targeting exosome nanoparticles activate Keap1 / Nrf2 / GPX4 signaling pathway to induce ferroptosis in osteosarcoma cells
Authors: Chen Wenkai , Li Zongguang , Yu Naichun , Zhang Linlin , Li Hongyu , Chen Yongjie , Gong Fengqing , Lin Wenping , He Xu , Wang Siyuan , Wu Yue , Ji Guangrong
Published: September 2023

Background

In recent years, the development of BMSCs-derived exosomes (EXO) for the treatment of osteosarcoma (OS) is a safe and promising modality for OS treatment, which can effectively deliver drugs to tumor cells in vivo. However, the differences in the drugs carried, and the binding of EXOs to other organs limit their therapeutic efficacy. Therefore, improving the OS-targeting ability of BMSCs EXOs and developing new drugs is crucial for the clinical application of targeted therapy for OS.

Results

In this study, we constructed a potential therapeutic nano platform by modifying BMSCs EXOs using the bone-targeting peptide SDSSD and encapsulated capreomycin (CAP) within a shell. These constructed nanoparticles (NPs) showed the ability of homologous targeting and bone-targeting exosomes (BT-EXO) significantly promotes cellular endocytosis in vitro and tumor accumulation in vivo. Furthermore, our results revealed that the constructed NPs induced ferroptosis in OS cells by prompting excessive accumulation of reactive oxygen species (ROS), Fe2+ aggregation, and lipid peroxidation and further identified the potential anticancer molecular mechanism of ferroptosis as transduced by the Keap1/Nrf2/GPX4 signaling pathway. Also, these constructed NP-directed ferroptosis showed significant inhibition of tumor growth in vivo with no significant side effects.

Conclusion

These results suggest that these constructed NPs have superior anticancer activity in mouse models of OS in vitro and in vivo, providing a new and promising strategy for combining ferroptosis-based chemotherapy with targeted therapy for OS.
The development of proximity labeling technology and its applications in mammals, plants, and microorganisms
Authors: Guo Jieyu , Guo Shuang , Lu Siao , Gong Jun , Wang Long , Ding Liqiong , Chen Qingjie , Liu Wu
Published: September 2023

Protein‒protein, protein‒RNA, and protein‒DNA interaction networks form the basis of cellular regulation and signal transduction, making it crucial to explore these interaction networks to understand complex biological processes. Traditional methods such as affinity purification and yeast two-hybrid assays have been shown to have limitations, as they can only isolate high-affinity molecular interactions under nonphysiological conditions or in vitro. Moreover, these methods have shortcomings for organelle isolation and protein subcellular localization. To address these issues, proximity labeling techniques have been developed. This technology not only overcomes the limitations of traditional methods but also offers unique advantages in studying protein spatial characteristics and molecular interactions within living cells. Currently, this technique not only is indispensable in research on mammalian nucleoprotein interactions but also provides a reliable approach for studying nonmammalian cells, such as plants, parasites and viruses. Given these advantages, this article provides a detailed introduction to the principles of proximity labeling techniques and the development of labeling enzymes. The focus is on summarizing the recent applications of TurboID and miniTurbo in mammals, plants, and microorganisms.
Simultaneous diagnosis of tuberculous pleurisy and malignant pleural effusion using metagenomic next-generation sequencing (mNGS)
Authors: Xu Fudong , Wang Qingfeng , Zhang Nana , Xing Xuya , Liu Zichen , Li Kun , Ma Yutong , Ou Qiuxiang , Jia Yaqiong , Chen Xuejing , Zhang Chen , Pan Junhua , Che Nanying
Published: September 2023

Background

Metagenomic next-generation sequencing (mNGS) has become a powerful tool for pathogen detection, but the value of human sequencing reads generated from it is underestimated.

Methods

A total of 138 patients with pleural effusion (PE) were diagnosed with tuberculous pleurisy (TBP, N = 82), malignant pleural effusion (MPE, N = 35), or non-TB infection (N = 21), whose PE samples all underwent mNGS analysis. Clinical TB tests including culture, Acid-Fast Bacillus (AFB) test, Xpert, and T-SPOT, were performed. To utilize mNGS for MPE identification, 25 non-MPE samples (20 TBP and 5 non-TB infection) were randomly selected to set human chromosome copy number baseline and generalized linear modeling was performed using copy number variant (CNV) features of the rest 113 samples (35 MPE and 78 non-MPE).

Results

The performance of TB detection was compared among five methods. T-SPOT demonstrated the highest sensitivity (61% vs. culture 32%, AFB 12%, Xpert 35%, and mNGS 49%) but with the highest false-positive rate (10%) as well. In contrast, mNGS was able to detect TB-genome in nearly half (40/82) of the PE samples from TBP subgroup, with 100% specificity. To evaluate the performance of using CNV features of the human genome for MPE prediction, we performed the leave-one-out cross-validation (LOOCV) in the subcohort excluding the 25 non-MPE samples for setting copy number standards, which demonstrated 54.1% sensitivity, 80.8% specificity, 71.7% accuracy, and an AUC of 0.851.

Conclusion

In summary, we exploited the value of human and non-human sequencing reads generated from mNGS, which showed promising ability in simultaneously detecting TBP and MPE.
Genetically proxied antidiabetic drugs targets and stroke risk
Authors: Zhu Yahui , Li Mao , Wang Hongfen , Yang Fei , Pang Xinyuan , Du Rongrong , Zhang Jinghong , Huang Xusheng
Published: September 2023

Background

Previous studies have assessed the association between antidiabetic drugs and stroke risk, but the results are inconsistent. Mendelian randomization (MR) was used to assess effects of antidiabetic drugs on stroke risk.

Methods

We selected blood glucose-lowering variants in genes encoding antidiabetic drugs targets from genome-wide association studies (GWAS). A two-sample MR and Colocalization analyses were applied to examine associations between antidiabetic drugs and the risk of stroke. For antidiabetic agents that had effect on stroke risk, an independent blood glucose GWAS summary data was used for further verification.

Results

Genetic proxies for sulfonylureas targets were associated with reduced risk of any stroke (OR=0.062, 95% CI 0.013-0.295, P=4.65×10－4) and any ischemic stroke (OR=0.055, 95% CI 0.010-0.289, P=6.25×10－4), but not with intracranial hemorrhage. Colocalization supported shared casual variants for blood glucose with any stroke and any ischemic stroke within the encoding genes for sulfonylureas targets (KCNJ11 and ABCC8) (posterior probability>0.7). Furthermore, genetic variants in the targets of insulin/insulin analogues, glucagon-like peptide-1 analogues, thiazolidinediones, and metformin were not associated with the risk of any stroke, any ischemic stroke and intracranial hemorrhage. The association was consistent in the analysis of sulfonylureas with stroke risk using an independent blood glucose GWAS summary data.

Conclusions

Our findings showed that genetic proxies for sulfonylureas targets by lowering blood glucose were associated with a lower risk of any stroke and any ischemic stroke. The study might be of great significance to guide the selection of glucose-lowering drugs in individuals at high risk of stroke.