bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue factor activates the coagulation cascade in mouse models of acute promyelocytic leukemia
Authors: Hisada Yohei , Kawano Tomohiro , Archibald Sierra J. , Welch John S. , Reeves Brandi N. , Mackman Nigel
Published: July 2023

Acute promyelocytic leukemia (APL) is associated with a high risk of bleeding and thrombosis. APL patients have an activated coagulation system, hyperfibrinolysis, and thrombocytopenia. APL cells express tissue factor (TF), a receptor and cofactor for factor VII/VIIa. This study had 2 goals. Firstly, we measured biomarkers of coagulation and fibrinolysis activation as well as platelet counts and bleeding in both mouse xenograft and allograft models of APL. Secondly, we determined the effect of inhibiting TF on the activation of coagulation in these models. We observed increased levels of plasma thrombin-antithrombin complexes (TAT), D-dimer, and plasmin-antiplasmin complexes, reduced platelet counts, and increased tail bleeding in both mouse models of APL. Fibrinogen levels decreased in the xenograft model but not in the allograft model. In contrast, the red blood cell count decreased in the allograft model but not in the xenograft model. Inhibition of APL-derived human TF with an anti-human TF monoclonal antibody reduced the level of TAT, increased platelet count, and normalized tail bleeding in a xenograft model. Inhibition of all sources of TF (APL cells and host cells) in the allograft model with a rat anti-mouse TF monoclonal antibody decreased the levels of TAT but did not affect the platelet count. Our study demonstrates that TF plays a central role in the activation of coagulation in both the xenograft and allograft mouse models of APL. These APL mouse models can be used to investigate the mechanisms of coagulopathy and thrombocytopenia in APL.
Heterologous production and secretion of active-form plant peroxidase in Brevibacillus choshinensis and their monolignol polymerization abilities analysis
Authors: Ishikura Hinako , Konishi Yuka , Miura Jun , Dohi Moeka , Kawai Shinya
Published: July 2023

Plant peroxidases are important for several processes, such as defense against pathogens, and auxin metabolism. In this study, we report the active production and secretion of plant peroxidase and mutated enzymes in the bacterium Brevibacillus choshinensis for the first time in the world. We introduced mutations into prxA3a, an anionic peroxidase gene of hybrid aspen, Populus × kitakamiensis, to substitute the amino acid residues at the surface of the protein and analyzed their modified substrate specificities. We have also reported heterologous expression of PrxA3a and mutated enzymes in yeast. Enzymes secreted in the culture medium by B. chosinensis were purified by Ni affinity chromatography, anion-exchange chromatography, and size-exclusion chromatography. The ability of the mutated enzymes to polymerize sinapyl alcohol, a monolignol, was higher than that of the wild-type enzyme. In particular, the FYAW-mutated enzyme produced by the bacterium showed higher polymerization activity, similar to that of the FYAW-mutated enzyme produced by yeast.
Physician-staffed prehospital units: a retrospective follow-up from an urban area in Scandinavia
Authors: Strandqvist Erik , Olheden Staffan , Bäckman Anders , Jörnvall Henrik , Bäckström Denise
Published: July 2023

Background

The aim of this study was to determine when and how rapid response vehicles (RRVs) make a difference in prehospital care by investigating the number and kinds of RRV assignment dispatches and the prehospital characteristics and interventions involved.

Methods

This retrospective cohort study was based on data from a quality assurance system where all assignments are registered. RRV staff register every assignment directly at the site, using a smartphone, tablet, or computer. There is no mandatory information requirement or time limit for registration. The study includes data for all RRVs operating in Region Stockholm, three during daytime hours and one at night – from January 1, 2021 to December 31, 2021.

Results

In 2021, RRVs in Stockholm were dispatched on 11,283 occasions, of which 3,571 (31.6%) resulted in stand-downs. In general, stand-downs were less common for older patients. The most common dispatch category was blunt trauma (1,584 or 14.0%), which accounted for the highest frequency of stand-downs (676 or 6.0%). The second most common category was cardiac arrest (1,086 or 9.6%), followed by shortness of breath (691 or 6.1%), medical not specified (N/S) (596 or 5.3%), and seizures (572 or 5.1%).

Conclusion

The study findings confirm that RRVs provide valuable assistance to the ambulance service in Stockholm, especially for cardiac arrest and trauma patients. In particular, RRV personnel have more advanced medical knowledge and can administer medications and perform interventions that the regular ambulance service cannot provide.
A novel nomogram and risk stratification system predicting the cancer-specific survival of patients with gastric neuroendocrine carcinoma: a study based on SEER database and external validation
Authors: Song Xue , Xie Yangyang , Lou Yafang
Published: July 2023

Background

Gastric neuroendocrine carcinoma (GNEC) is a rare histology of gastric cancer. The retrospective study was designed to construct and validate a nomogram for predicting the cancer-specific survival (CSS) of postoperative GNEC patients.

Methods

Data for 28 patients from the Hangzhou TCM Hospital were identified as the external validation cohort. A total of 1493 patients were included in the SEER database and randomly assigned to the training group (1045 patients) and internal validation group (448 patients). The nomogram was constructed using the findings of univariate and multivariate Cox regression studies. The model was evaluated by consistency index (C-index), calibration plots, and clinical net benefit. Finally, the effect between the nomogram and AJCC staging system was compared by net reclassification index (NRI) and integrated discrimination improvement (IDI).

Results

Age, gender, grade, T stage, N stage, metastasis, primary site, tumor size, RNE, and chemotherapy were incorporated in the nomogram. The C-indexes were 0.792 and 0.782 in the training and internal verification sets. The 1-, 3-, and 5-year CSS predicted by the nomogram and actual measurements had good agreement in calibration plots. The 1-, 3-, and 5-year NRI were 0.21, 0.29, and 0.37, respectively. The 1-, 3-, and 5-year IDI values were 0.10, 0.12, and 0.13 (P < 0.001), respectively. In 1-, 3-, and 5-year CSS prediction using DCA curves, the nomogram outperformed the AJCC staging system. The nomogram performed well in both the internal and external validation cohorts.

Conclusion

We developed and validated a nomogram to predict 1-, 3-, and 5-year CSS for GNEC patients after surgical resection. This well-performing model could help doctors enhance the treatment plan.
A population-based cohort study on changes in breast, lung and colorectal cancer incidence and mortality among non-Western immigrant women
Authors: Lamminmäki Maarit , Leivonen Aku , Heinävaara Sirpa , Nygård Mari , Ursin Giske , Campbell Suzanne , Stefansdóttir Hrefna , Hirvonen Elli , Toikkanen Salla , Vejborg Ilse Merete Munk , Njor Sisse Helle , Sarkeala Tytti
Published: July 2023

Background

Cancer risk varies geographically, and migrants are influenced by different risk factors before, during and after migration. Increased migration from non-Western countries to the Nordic countries calls for a better understanding of the migrants’ cancer risk and the change in risk patterns over time. The aim of this study was to compare the incidence and mortality of breast, colorectal and lung cancer between non-Western immigrant and the native female population in Denmark, Finland, Iceland, and Norway.

Material and methods

Data from national registries were processed and pre-analysed in each country. Multivariate Poisson regression models were used to model the relative differences in incidence and mortality as rate ratios (RR). The country-specific estimates and summary statistics were pooled together using a random effects model.

Results

Non-Western immigrant women had significantly lower breast (RR 0.71, 0.65–0.78), colorectal (RR 0.72, 0.57–0.92) and lung (RR 0.55, 0.42–0.72) cancer incidence rates than native women, and the risk of these cancers among immigrant women increased with duration of residence. Differences were parallel in breast, colorectal and lung cancer mortality (RR 0.64, 0.55–0.74; RR 0.66, 0.48–0.92; RR 0.51, 0.34–0.79). Among immigrant women, higher education increased the risk for breast cancer and decreased it for lung cancer.

Conclusion

The results significantly complement and add to the previous findings of cancer burden and cancer burden transition among migrants and provide evidence of a prolonged cancer risk advantage among non-Western immigrant women. However, the findings show an increasing risk of lifestyle-related cancers with increasing duration of residence in the host country. Further studies are needed to discover underlying reasons for this phenomenon.
Severe macular complications in glaucoma: high-resolution multimodal imaging characteristics and review of the literature
Authors: Lama Hugo , Pâques Michel , Brasnu Emmanuelle , Vu Jade , Chaumette Céline , Dupas Bénédicte , Fardeau Christine , Chehaibou Ismaël , Rouland Jean-François , Besombes Guillaume , Labetoulle Marc , Labbé Antoine , Rousseau Antoine
Published: July 2023

Purpose

To describe imaging characteristics of severe macular complications occurring in glaucoma and discuss available treatments.

Methods

Retrospective case series of glaucomatous patients with macular retinoschisis (MR) and/or serous retinal detachment (SRD). Patients underwent a complete ophthalmological examination and multimodal imaging including retinography, SD-OCT, fluorescein and indocyanine green angiography (FA & ICGA) and adaptive optics (AO).

Results

Ten eyes (8 patients) were included. Initial BCVA was 1.04 ± 1.12 logMAR and IOP was 24.0 ± 9.3mmHg. All eyes presented with MR while SRD was present in 5 eyes (5 patients), with a central macular thickness of 573 ± 152 μm. FA and ICGA allowed to exclude leakage in all cases. A focal lamina cribrosa defect (LCD) was found in four eyes (4 patients) using OCT, with AO providing en-face visualization of the defect in one eye. Outer retinal hole was present in 3 eyes (3 patients). No visual improvement or resolution of the macular retinoschisis was observed in eyes with medical or surgical IOP control (N = 9). Vitrectomy with internal membrane limiting peeling and gas tamponade was performed in one eye with good visual results.

Conclusions

Multimodal high-resolution imaging is essential to diagnose severe macular complications associated with advanced glaucoma.
The efficacy and safety of varenicline nasal spray for the management of dry eye signs: a systematic review and meta-analysis
Authors: Bashrahil Bader , Taher Nada , Alzahrani Ziyad , Alnabihi Ahmed , Aldahlawi Abdulaziz , Alkhathlan Mohammed , Alghamdi Saeed
Published: July 2023

Background

Dry eye disease (DED) is caused by a persistently unstable tear film leading to ocular discomfort and is treated mainly with tear supplementation. There is emerging evidence that nicotinic acetylcholine receptor (nAChR) agonists (e.g., varenicline and simpinicline) nasal sprays are effective for DED. Our systematic review and meta-analysis assessed the efficacy and safety of varenicline nasal spray (VNS) for DED treatment.

Methods

The Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched. Only randomized controlled trials (RCTs) that evaluated the efficacy of VNS versus placebo were included. The efficacy endpoint was the mean change in the anesthetized Schirmer test score (STS), a measure of basal tear production, from baseline. The safety endpoints were serious adverse events (SAEs) and adverse events (AEs). The standardized mean difference (SMD) was used for continuous outcomes, while the risk ratio (RR) was used to demonstrate dichotomous variables. The certainty of the evidence was rated utilizing the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The risk of bias assessment was conducted using the Revised Cochrane risk of bias tool for randomized trials.

Results

Three RCTs (n = 1063) met the eligibility criteria. All RCTs had a low risk of bias. The meta-analysis found a statistically significant increase in the mean STS change from baseline on day 28. The pooled analysis found no significant difference between VNS and placebo in the frequency of SAEs and ocular AEs. However, VNS had a significant effect on developing nasal cavity-related AEs.

Conclusion

VNS caused a highly significant improvement regarding the efficacy endpoint but caused an increased frequency of some nasal cavity-related AEs (i.e., cough and throat irritation). However, it caused neither SAEs nor ocular AEs. Included studies had a low risk of bias.
The impact of neighborhood mental health on the mental health of older adults
Authors: Gong Rengui , Xia Dongping , Hu Zan , Hu Yangming
Published: July 2023

Background

In this article, we use cross-sectional data obtained from the 2018 China Health and Aging Tracking Survey (CHARLS) to examine the impact of neighborhood mental health at the community level on the mental health of older adults aged 60 years and older.

Methods

NMH is the average mental health of older adults in the same community, excluding the older adults themselves. The explained variable mental health in this paper was measured using the simple CES-D depression scale. The mediating variables were social connectedness, social participation and social inclusion, and the instrumental variables were physical exercise and amusement. regression analysis was conducted using OLS regression models, two-stage least squares (IV-2SLS) instrumental variables to address the two-way causality of NMH and MH, and KHB decomposition was used to investigate the effect mechanism.

Results

Baseline regressions showed that the neighborhood mental health effect positively influenced the mental health of older adults (Coef. = 0.356, 95% CI 0.315,0.397). The neighborhood mental health effect estimated by IV-2SLS (Coef. = 0.251, 95% CI 0.096,0.405) was higher than the OLS regression, indicating endogeneity. The mediated effects of KHB showed total (Coef. = 0.356, 95% CI 0.314,0.398), direct (Coef. = 0.281, 95% CI 0.232,0.330), and indirect effects (Coef. = 0.075, 95% CI 0.049,0.101). While the total effect was 1.266 times higher than the direct effect, 21.03% of the total effect came from mediating variables.

Conclusions

First, the neighborhood mental health effect has a positive impact on the mental health of older adults, but there are heterogeneous differences based on gender, age, and place of residence. Second, the results of the IV-2SLS estimation showed that the effect of the neighborhood mental health effect was underestimated if endogenous problems were not controlled for. Third, the effect of neighborhood mental health on older adults' mental health was tested to be stable. Moreover, social connectedness, social participation, and social interaction are important mediating mechanisms for the effect of neighborhood mental health on older adults' mental health. This study provides new perspectives and ideas for an in-depth understanding of the mental health of older adults in the context of social transformation in China.
Effectiveness of health promotion intervention on the knowledge and selected practices related with oral cancer among a group of vulnerable youth in Sri Lanka
Authors: Dhanapriyanka Manori , RDFC Kanthi , Jayasekara Prasanna
Published: July 2023

Background

There has been a noticeable trend of younger people being diagnosed with oral cancer, particularly among those from low socio-economic backgrounds. Poor knowledge on risk factors toward oral cancer and the growing fashion of using tobacco also identified among younger generation. Present study aimed to assess the effectiveness of a health promotion intervention to improve the knowledge and encourage positive practices associated with oral cancer among a group of vulnerable youth in Sri Lanka.

Methods

The study was a community based quasi experimental study, conducted in urban slums in the district of Colombo, Sri Lanka. Sample size for one group was 120 youth participants aged between 15 and 24 years. Health promotion intervention was implemented to the intervention group and follow up period was 6 months. The control group did not receive the intervention. Awareness of oral cancer and oral potentially malignant disorders, tobacco chewing practice (betel quid chewing and commercially prepared tobacco and areca nut packet (CPTAP) chewing) and self-mouth examination practice were assessed at the beginning and after 6 months in both groups using an interviewer administered questionnaire. Changes in the knowledge, self-mouth examination practice, quit rate and fresh up take rate were computed to determine the effectiveness.

Results

There was no loss to follow up. No significant difference was observed between the groups in pre intervention assessment regarding the knowledge, tobacco chewing and self-mouth examination practices. Knowledge score was significantly differed between the groups P = 0.000 in the post intervention assessment as well as among females P = 0.001. Quit rate of the tobacco chewing practice, betel chewing practice and CPTAP chewing practice among intervention group was 33%, 70%, and 13% respectively while control group did not have any quitters, P = 0.001. Fresh up take rate of tobacco chewing in the intervention group was 6.7% compared to the 37.5% in the control group, P = 0.001. Practicing self-mouth examination was significantly higher in intervention group in post intervention assessment, P = 0.000.

Conclusion

Multicomponent health promotion intervention (Advocacy, Interactive discussions, IEC materials and Community mobilization) was significantly effective in enhancing the knowledge, increasing self-mouth examination practice, and reducing tobacco chewing practice among a vulnerable group of youth in Sri Lanka.
Abnormal adenosine metabolism of neutrophils inhibits airway inflammation and remodeling in asthma model induced by Aspergillus fumigatus
Authors: Liu Ting-ting , Wang Yue-li , Zhang Zhi , Jia Li-xin , Zhang Jing , Zheng Shuai , Chen Zhi-hua , Shen Hua-hao , Piao Chun-mei , Du Jie
Published: July 2023

Background

Neutrophils consume a large amount of energy when performing their functions. Compared with other white blood cells, neutrophils contain few mitochondria and mainly rely on glycolysis and gluconeogenesis to produce ATP. The inflammatory site is hypoxic and nutrient poor. Our aim is to study the role of abnormal adenosine metabolism of neutrophils in the asthmatic airway inflammation microenvironment.

Method

In this study, an asthma model was established by intratracheal instillation of Aspergillus fumigatus extract in Ecto-5'-Nucleotidase (CD73) gene–knockout and wild-type mice. Multiple analyses from bronchoalveolar lavage fluid (BALF) were used to determine the levels of cytokines and chemokines. Immunohistochemistry was used to detect subcutaneous fibrosis and inflammatory cell infiltration. Finally, adenosine 5’-(α, β-methylene) diphosphate (APCP), a CD73 inhibitor, was pumped subcutaneously before Aspergillus attack to observe the infiltration of inflammatory cells and subcutaneous fibrosis to clarify its therapeutic effect.

Result

PAS staining showed that CD73 knockout inhibited pulmonary epithelial cell proliferation and bronchial fibrosis induced by Aspergillus extract. The genetic knockdownof CD73 significantly reduced the production of Th2 cytokines, interleukin (IL)-4, IL-6, IL-13, chemokine (C–C motif) ligand 5 (CCL5), eosinophil chemokine, neutrophil IL-17, and granulocyte colony-stimulating factor (G-CSF). In addition, exogenous adenosine supplementation increased airway inflammation. Finally, the CD73 inhibitor APCP was administered to reduce inflammation and subcutaneous fibrosis.

Conclusion

Elevated adenosine metabolism plays an inflammatory role in asthma, and CD73 could be a potential therapeutic target for asthma.
Mandibular third molar extraction: perceived surgical difficulty in relation to professional training
Authors: Sánchez Jorge María Isabel , Ocaña Rosa Acevedo , Valle Rodríguez Carolina , Peyró Fernández-Montes Barbara , Rico-Romano Cristina , Bazal-Bonelli Santiago , Sánchez-Labrador Luis , Cortés-Bretón Brinkmann Jorge
Published: July 2023

Background

Establishing the level of surgical difficulty pre-operatively is an essential step in ensuring correct treatment planning. This study set out to determine whether the knowledge and experience acquired by dentists who had received different levels of training influenced, firstly, the perceived levels of difficulty of a variety of cases of mandibular third molar (MTM) extraction and, secondly, the perceived difficulty deriving from a series of factors (patient-related factors, anatomical and radiographic factors, operative factors).

Methods

This cross-sectional, descriptive, observational study took the form of a survey. Using a visual analog scale (VAS), participants evaluated both the perceived difficulty of 30 cases of MTM extraction described by means of digital panoramic radiographs and the perceived difficulty deriving from a series of factors conditioning MTM extraction. The results underwent statistical analysis with SPSS Statistics 28.0 software. Non-parametric tests (Mann Whitney test for independent samples and the Kruskal–Wallis test) were applied.

Results

A total of 389 surveys were available for analysis. Dental practioners with no surgical training saw the intervention as presenting greater difficulty. Professionals with postgraduate training in oral surgery considered patient-related factors more important than operative factors, in contrast to dentists who had not received oral surgery training.

Conclusions

Dental training has a signficant influence on the perceived difficulty of MTM extraction and also affects opinions about which factors have greater or lesser influence on surgical difficulty.
Effectiveness of SBAR-based simulation programs for nursing students: a systematic review
Authors: Yun Jungmi , Lee Yun Ji , Kang Kyoungrim , Park Jongmin
Published: July 2023

Background

Situation, background, assessment, and recommendation (SBAR) has been extensively used in clinical and nursing education. A structured communication program increases effective communication, positivity, and education satisfaction during inter-professional collaboration among nursing students. This systematic review aimed to identify and synthesize evidence on the effectiveness of SBAR-based simulation training for nursing students.

Methods

A research protocol was developed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. The protocol for this study was registered in PROSPERO (CRD42021234068). Eight bibliographical databases were searched for studies published between 2001 and 2021, using relevant search terms. Searches were conducted in PubMed, Embase, Cumulative Index to Nursing and Allied Health, and Cochrane Central Register of Controlled Trials for literature in English, and DBpia, Research Information Sharing Service, Korean Studies Information Service System, and Korea Institute of Science and Technology Information for literature in Korean. After screening titles, abstracts, and full-text papers, pertinent data were extracted, and critical appraisals of the retrieved studies were performed. Data were analyzed using the framework approach, and the findings were presented in a narrative summary. The Effective Public Health Practice Project “Quality Assessment Tool for Quantitative Studies” was used to assess the quality of the included studies.

Results

Twelve studies were included: 3 randomized controlled trials and 9 quasi-experimental studies. Two overarching themes were noted, namely communication clarity and critical thinking. The results of six out of 12 studies produced significant results in favor of SBAR-based simulation in terms of communication clarity. Divergent results were obtained regarding communication ability, critical thinking, confidence, learning self-efficacy, and attitude toward patient safety. The results of these studies highlight that communication clarity ultimately leads to positive results in terms of nursing students’ behaviors related to patient safety.

Conclusions

This review provides a comprehensive update of the literature on the effectiveness of SBAR-based nursing simulation programs for nursing students. These programs were found to have positive learning outcomes because of clear and concise communication. Further studies on the effectiveness of various learning outcomes derived from SBAR-based programs are required.
Tumor-derived small extracellular vesicles promote breast cancer progression by upregulating PD-L1 expression in macrophages
Authors: Xu Di , Chen Wen-Quan , Liang Ming-Xing , Chen Xiu , Liu Zhen , Fei Yin-Jiao , Shao Xin-Yi , Wu Yang , Zhang Wei , Tang Jin-Hai
Published: July 2023

Background

The metastasis of breast cancer (BC) is a complex multi-step pathological process, strictly dependent on the intrinsic characteristics of BC cells and promoted by a predisposing microenvironment. Although immunotherapy has made important progress in metastasis BC, the heterogeneity of PD-L1 in tumor associated macrophages (TAMs) in BC and the underlying mechanisms in the metastasis development of BC are still not completely elucidated. Small extracellular vesicles (sEVs) represent essential interaction mediators between BC cells and TAMs. It is worth noting to explore the underlying mechanisms typical of sEVs and their role in the metastasis development of BC.

Methods

The structure of sEVs was identified by TEM, while the particle size and amounts of sEVs were detected by BCA and NTA analysis. The specific PD-L1 + CD163 + TAM subpopulation in metastasis BC was identified by scRNA-seq data of GEO datasets and verified by IHC and IF. The function of TAMs and sEVs in metastasis BC was explored by RT-qPCR, WB, IF, flow cytometry and in vivo experiment. The expression profiles of plasma sEVs-miRNA in relation to BC metastasis was analyzed using next-generation sequencing. Further detailed mechanisms of sEVs in the metastasis development of BC were explored by bioinformatics analysis, RT-qPCR, WB and luciferase reporter assay.

Results

In this study, we identified that the immunosuppressive molecule PD-L1 was more abundant in TAMs than in BC cells, and a specific PD-L1 + CD163 + TAM subpopulation was found to be associated with metastasis BC. Additionally, we found that BC cells-derived sEVs can upregulate the PD-L1 expression and induce the M2 polarization, enhancing the metastasis development both in vitro and in vivo. Also, Clinical data showed that sEV-miR-106b-5p and sEV-miR-18a-5p was in relation to BC metastasis development and poor prognosis of BC patients. Further mechanistic experiments revealed that BC-derived sEV-miR-106b-5p and sEV-miR-18a-5p could synergistically promoted the PD-L1 expression in M2 TAMs by modulating the PTEN/AKT and PIAS3/STAT3 pathways, resulting in the enhancement of the BC cells invasion and metastasis.

Conclusions

Our study demonstrated that BC-derived sEVs can induce metastasis in BC through miR-106b-5p/PTEN/AKT/PD-L1 and miR-18a-5p/PIAS3/STAT3/PD-L1 pathways in TAMs. Therefore, the inhibition of these specific interactions of signaling pathways would represent a promising target for future therapeutic strategies for treatment of BC.
Docosahexaenoic acid-rich algae oil supplementation in mothers of preterm infants is associated with a modification in breast milk oxylipins profile
Authors: Fougère Hélène , Greffard Karine , Guillot Mireille , Rudkowska Iwona , Pronovost Etienne , Simonyan David , Marc Isabelle , Bilodeau Jean-François
Published: July 2023

Oxylipins are derived from enzymatic and non-enzymatic oxidation of n-3 and n-6 long-chain polyunsaturated fatty acids. They are known to be involved in inflammatory processes. The aim of this study was to describe the breast milk oxylipin profile following a docosahexaenoic acid (DHA) supplementation of mothers of preterm infants. We examined the oxylipins profile in breast milk collected at day 14 post-delivery, of 40 mothers who delivered before 29 weeks of gestation and who were supplemented with either DHA-rich algae oil (S-DHA) or a placebo (PL). These mothers were selected from the MOBYDIck cohort (NCT02371460 registered on 25/05/2015 in ClinicalTrials.gov) according to the supplementation received (S-DHA vs. PL) and the DHA content quartiles as measured in breast milk (Low vs. High) to generate four study groups. Milk oxylipins, as ng/mL of milk, were analyzed by LC-MS/MS. Ten oxylipins derived from DHA were higher in the S-DHA-High group than the other three groups (P < 0.001). The 18-HEPE, was also higher in the S-DHA-High group (0.11 ± 0.01) compared to the other groups (P = 0.0001). Compared to the PL-Low group, there was a reduction in pro-inflammatory prostaglandins found in the S-DHA-High group with lower levels of prostaglandins PGF2α (0.21 ± 0.45 in the S-DHA-High group vs. 1.87 ± 0.44 in the PL-Low group, P = 0.03) and of PGE2 (0.33 ± 0.26 in the S-DHA-High group vs. 1.28 ± 0.25 in the PL-Low group, P = 0.04).In sum, the DHA supplementation was linked with a predominance of anti-inflammatory oxylipins in breast milk of mothers who delivered very preterm, like 17(S)-HDHA and 18-HEPE, precursors of D and E resolvins respectively. This was also accompanied with a lower level of pro-inflammatory prostaglandins.
The layered crisis of the primary care medical workforce in the European region: what evidence do we need to identify causes and solutions?
Authors: Russo Giuliano , Perelman Julian , Zapata Tomas , Šantrić-Milićević Milena
Published: July 2023

Primary care services are key to population health and for the efficient and equitable organisation of national health systems. This is why they are often financed through public funds. Primary care doctors are instrumental for the delivery of preventive services, continuity of care, and for the referral of patients through the system. These cadres are also the single largest health expenditure at the core of such services. Although recruitment and retention of primary care doctors have always been challenging, shortages are now exacerbated by higher demand for services from aging populations, increased burden of chronic diseases, backlogs from the COVID-19 pandemic, and patient expectations. At the same time, the supply of primary care physicians is constrained by rising retirement rates, internal and external migration, worsening working conditions, budget cuts, and increased burnout. Misalignment between national education sectors and labour markets is becoming apparent, compounding staff shortages and maldistribution. With their predominantly publicly funded health systems and in the aftermath of COVID-19, countries of the European region appear to be now on the cusp of a multi-layered, slow-burning primary care crisis, with almost every country reporting long waiting lists for doctor appointments, shortages of physicians, unfilled vacancies, and consequently, added pressures on hospitals’ Accident and Emergency services. This articles collection aims at pulling together the evidence from countries of the European Region on root causes of such workforce crisis, impacts, and effectiveness of existing policies to mitigate it. Original research is needed, offering analysis and fresh insights into the primary care medical workforce crisis in wider Europe. Ultimately, the aim of this articles collection is to provide an evidence basis for the identification of policy solutions to present and future primary health care crises in high as well as lower-income countries.
Time spent in a better cardiovascular health and risk of cardiovascular diseases and mortality: a prospective cohort study
Authors: Tian Qiuyue , Chen Shuohua , Meng Xiaoni , Wang Haotian , Li Cancan , Zheng Deqiang , Wu Lijuan , Wang Aitian , Wu Shouling , Wang Youxin
Published: July 2023

Background

The protective effect of a higher ideal cardiovascular health (CVH) score on cardiovascular diseases (CVDs) and mortality is well recognized. However, little is known regarding the length of favorable CVH status associated with CVDs and mortality. This study aimed to examined whether the duration of better (ideal or intermediate) CVH is associated with risk of developing CVDs and mortality.

Methods

This prospective cohort study used data from 83,536 individuals from 2006 to 2020 who were enrolled in the Kailuan Study. The CVH scores of individuals were assessed at visits 1, 2, 3, and 4, respectively. The years spent in better CVH were estimated for each individual as the number of examination cycles (0–4) in which the participant was in that CVH score ≥ 8 multiplied by 2 (the mean year interval of each visit). The primary outcomes are CVD events and all-cause mortality.

Results

After a median follow-up period of 7.48 years, 5486 (7.07%) cases of incident CVD events and 7669 (9.18%) deaths occurred. Compared with participants in “ ≤ 4 years” group, those who maintained for > 4 years had less likely to develop adverse outcomes (CVD events: hazard ratio (HR): 0.60, 95% confidence interval (CI 0.56–0.63; all-cause mortality: HR: 0.77, 95% CI 0.74–0.81). The number of years spent in better CVH was nonlinearly correlated with CVD events or mortality (all Ps for nonlinear < 0.05). The results indicated that maintaining more than 6 years in a better CVH status was associated with a decreased risk of CVD events or mortality.

Conclusion

Our study indicates that individuals maintaining more than 6 years in better CVH could increase cardiometabolic benefits and a lower risk of all-cause mortality.
Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation
Authors: Chen Yijun , Yu Yang
Published: July 2023

Alzheimer’s Disease (AD) contributes to most cases of dementia. Its prominent neuropathological features are the extracellular neuritic plaques and intercellular neurofibrillary tangles composed of aggregated β-amyloid (Aβ) and hyperphosphorylated tau protein, respectively. In the past few decades, disease-modifying therapy targeting Aβ has been the focus of AD drug development. Even though it is encouraging that two of these drugs have recently received accelerated US Food and Drug Administration approval for AD treatment, their efficacy or long-term safety is controversial. Tau has received increasing attention as a potential therapeutic target, since evidence indicates that tau pathology is more associated with cognitive dysfunction. Moreover, inflammation, especially neuroinflammation, accompanies AD pathological processes and is also linked to cognitive deficits. Accumulating evidence indicates that inflammation has a complex and tight interplay with tau pathology. Here, we review recent evidence on the interaction between tau pathology, focusing on tau post-translational modification and dissemination, and neuroinflammatory responses, including glial cell activation and inflammatory signaling pathways. Then, we summarize the latest clinical trials targeting tau and neuroinflammation. Sustained and increased inflammatory responses in glial cells and neurons are pivotal cellular drivers and regulators of the exacerbation of tau pathology, which further contributes to its worsening by aggravating inflammatory responses. Unraveling the precise mechanisms underlying the relationship between tau pathology and neuroinflammation will provide new insights into the discovery and clinical translation of therapeutic targets for AD and other tau-related diseases (tauopathies). Targeting multiple pathologies and precision therapy strategies will be the crucial direction for developing drugs for AD and other tauopathies.
The orthodontic implant site-switching technique: a preliminary study in dogs
Authors: Lu Meng , Li Weixu , Wang Yeqing , Yuan Lixian , Cao Meng
Published: July 2023

Background

To evaluate the quantity and quality of bone in the newly formed edentulous area produced by the orthodontic implant site-switching technique.

Methods

The bilateral maxillary first premolars of five beagle dogs were extracted and bone defects were created. The right and left sides of the maxilla were randomly divided into control and experimental sides. On the experimental side, the maxillary second premolar was mesially moved into the position of the missing first premolar. On the control side, the second maxillary premolar was extracted. Six months later, the beagles were euthanized. Microcomputer tomography was used to analyze bone microstructure parameters, alveolar bone height and alveolar bone width of the regenerated bone. Histological analysis was performed by staining tissue sections with toluidine blue.

Results

Median BV/TV values in the experimental group (81.78%) were significantly larger than those in the control group (35.67%; p = 0.04). Median Tb.Sp values in the experimental group (0.14 mm) were significantly lower than those in the control group (0.54 mm; p = 0.04). Median Tb.Th values in the experimental group (0.48 mm) were significantly higher than those in the control group (0.21 mm; p = 0.04). Median Tb.Pf values in the experimental group (0.65/mm) were significantly lower than those in the control group (3.15/mm; p = 0.04). There was no significant difference in the trabecular number (Tb.N) between the two groups (p = 0.23). The median alveolar bone height values in the experimental group (-0.81 mm) were significantly higher than those in the control group (-2.11 mm; p = 0.04) at a distance 5 mm from the mesial CEJ of the third premolar. The median alveolar bone height values in the experimental group (0.45 mm) were significantly higher than those in the control group (-1.70 mm; p = 0.04) at a distance 6 mm from the mesial CEJ of the third premolar. There was no significant difference in alveolar bone width when compared between the two groups (p > 0.05).

Conclusions

The newly formed edentulous area created by orthodontic treatment had more compact and thicker trabeculae than the extraction socket. Furthermore, the newly formed edentulous area had a greater alveolar bone height available for the placement of implants.
Advances of medical nanorobots for future cancer treatments
Authors: Kong Xiangyi , Gao Peng , Wang Jing , Fang Yi , Hwang Kuo Chu
Published: July 2023

Early detection and diagnosis of many cancers is very challenging. Late stage detection of a cancer always leads to high mortality rates. It is imperative to develop novel and more sensitive and effective diagnosis and therapeutic methods for cancer treatments. The development of new cancer treatments has become a crucial aspect of medical advancements. Nanobots, as one of the most promising applications of nanomedicines, are at the forefront of multidisciplinary research. With the progress of nanotechnology, nanobots enable the assembly and deployment of functional molecular/nanosized machines and are increasingly being utilized in cancer diagnosis and therapeutic treatment. In recent years, various practical applications of nanobots for cancer treatments have transitioned from theory to practice, from in vitro experiments to in vivo applications. In this paper, we review and analyze the recent advancements of nanobots in cancer treatments, with a particular emphasis on their key fundamental features and their applications in drug delivery, tumor sensing and diagnosis, targeted therapy, minimally invasive surgery, and other comprehensive treatments. At the same time, we discuss the challenges and the potential research opportunities for nanobots in revolutionizing cancer treatments. In the future, medical nanobots are expected to become more sophisticated and capable of performing multiple medical functions and tasks, ultimately becoming true nanosubmarines in the bloodstream.

Graphical abstract
Mathematical processing of absorption as green smart spectrophotometric methods for concurrent assay of hepatitis C antiviral drugs, Sofosbuvir and Simeprevir: application to combined pharmaceutical dosage forms and evaluation of the method greenness
Authors: Derayea Sayed M. , Abu-hassan Ahmed A. , Hamad Ahmed A. , Eltoukhi Walid E. , Hamad Amal E. , Mohammed Bassam Shaaban
Published: July 2023

The present work was developed to create three rapid, simple, eco-friendly, cheap spectrophotometric methods for concurrent assay of Sofosbuvir (SOF) and Simeprevir (SMV) in their pure, laboratory prepared mixture and pharmaceutical dosage form with high degree of accuracy and precision. Three methods were developed including iso-absorptive point, ratio subtraction and dual wavelength. The linear range of the proposed methods was 3.0–50.0 and 2.0–50.0 µg mL−1 for SMV and SOF, respectively. The proposed methods were validated according to ICH guidelines in terms of linearity, accuracy, precision, limit of detection and limit of quantitation. The proposed approach is highly simple and the procedure is environmentally green making it suitable for the drug analysis in routine works.
Three Gorges Dam: Potential differential drivers and trend in the spatio-temporal evolution of the change in snail density based on a Bayesian spatial–temporal model and 5-year longitudinal study
Authors: Gong Yanfeng , Tong Yixin , Jiang Honglin , Xu Ning , Yin Jiangfan , Wang Jiamin , Huang Junhui , Chen Yue , Jiang Qingwu , Li Shizhu , Zhou Yibiao
Published: July 2023

Background

Snail abundance varies spatially and temporally. Few studies have elucidated the different effects of the determinants affecting snail density between upstream and downstream areas of the Three Gorges Dam (TGD). We therefore investigated the differential drivers of changes in snail density in these areas, as well as the spatial–temporal effects of these changes.

Methods

A snail survey was conducted at 200 sites over a 5-year period to monitor dynamic changes in snail abundance within the Yangtze River basin. Data on corresponding variables that might affect snail abundance, such as meteorology, vegetation, terrain and economy, were collected from multiple data sources. A Bayesian spatial–temporal modeling framework was constructed to explore the differential determinants driving the change in snail density and the spatial–temporal effects of the change.

Results

Volatility in snail density was unambiguously detected in the downstream area of the TGD, while a small increment in volatility was detected in the upstream area. Regarding the downstream area of the TGD, snail density was positively associated with the average minimum temperature in January of the same year, the annual Normalized Difference Vegetation Index (NDVI) of the previous year and the second, third and fourth quartile, respectively, of average annual relative humidity of the previous year. Snail density was negatively associated with the average maximum temperature in July of the previous year and annual nighttime light of the previous year. An approximately inverted “U” curve of relative risk was detected among sites with a greater average annual ground surface temperature in the previous year. Regarding the upstream area, snail density was positively associated with NDVI and with the second, third and fourth quartile, respectively, of total precipitation of the previous year. Snail density was negatively associated with slope.

Conclusions

This study demonstrated a rebound in snail density between 2015 and 2019. In particular, temperature, humidity, vegetation and human activity were the main drivers affecting snail abundance in the downstream area of the TGD, while precipitation, slope and vegetation were the main drivers affecting snail abundance in the upstream area. These findings can assist authorities to develop and perform more precise strategies for surveys and control of snail populations.

Graphical Abstract
Daily socket comfort in transtibial amputee with a vacuum-assisted suspension system: study protocol of a randomized, multicenter, double-blind multiple N-of-1 trial
Authors: Klotz Rémi , Emile Guilhem , Daviet Jean-Christophe , De Sèze Mathieu , Godet Julien , Urbinelli Renaud , Krasny-Pacini Agata
Published: July 2023

Background

The main aim of this paper is to present the feasibility of rigorously designed multiple N-of-1 design in prosthetics research. While research of adequate power and high quality is often lacking in rehabilitation, N-of-1 trials can offer a feasible alternative to randomized controlled group trials, both increasing design power at group level and allowing a rigorous, statistically confirmed evaluation of effectiveness at a single patient level. The paper presents a multiple N-of-1 trial protocol, which aim is to evaluate the effectiveness of Unity, a prosthetic add-on suspension system for amputees, on patient-reported comfort during daily activities (main outcome measure), prosthesis wearing time, perception of limb-prosthesis fitting and stump volume and functional walking parameters.

Methods

Multicenter, randomized, prospective, double-blind multiple N-of-1 trial using an introduction/withdrawal design alternating Unity connected/disconnected phases of randomized length on twenty patients with unilateral transtibial amputation. The primary outcome measure is the Prosthetic Socket Comfort Score (SCS), a validated measure of comfort, administered daily by an phone app designed for the study. Secondary outcomes measures will be collected during the 50 days period of the N-of-1 trial: (1) by the same app, daily for patient-reported limb-prosthesis fitting, stump volume variation, and daily wearing time of the prosthesis; (2) by a pedometer for the number of steps per day; (3) by blind assessors in the rehabilitation center during adjustment visits for functional walking parameter (L-Test, 6-minute walk test), and by the patient for the QUEST, and ABC-S. Effectiveness of the Unity system regarding SCS and daily secondary outcome measures will be tested by randomization test. The secondary outcome measures assessed during visits in the rehabilitation center will be analyzed by Non Overlap of All pairs. An estimate of the effect on the amputee population will be generated by aggregating each individual clinical trial (N-of-1 trial) by Hierarchical Bayesian methods.

Discussion

This study protocol was designed to answer the question “which device is best for THIS patient" and to conclude at a group level on the effectiveness of a new devic, using a Multiple N-of-1 trial, which is promising but underused in prosthetics research so far.

Trial registration

N° ID-RCB 2020-A01309-30 Clintrial.gov : NCT04804150 - Retrospectively registered March 20th 2021.