bluuebunny/crossref_metadata_2025 huggingface dataset:
Bio-guided isolation of potential anti-inflammatory constituents of some endophytes isolated from the leaves of ground cherry (Physalis pruinosa L.) via ex-vivo and in-silico studies
Authors: Mahana Asmaa , Hammoda Hala M. , Saad Mona M. G. , Radwan Mohamed M. , ElSohly Mahmoud A. , Ghareeb Doaa A. , Harraz Fathallah M. , Shawky Eman
Published: April 2023

Background

Due to the extensive potential of previously studied endophytes in addition to plants belonging to genus Physalis as a source of anti-inflammatory constituents, the present study aimed at isolation for the first time some endophytic fungi from the medicinal plant Physalis pruinosa.

Methods

The endophytic fungi were isolated from the fresh leaves of P. pruinosa then purified and identified by both morphological and molecular methods. Comparative evaluation of the cytotoxic and ex vivo anti-inflammatory activity in addition to gene expression of the three pro-inflammatory indicators (TNF-α, IL-1β and INF-γ) was performed in WBCs treated with lipopolysaccharide (LPS) for the identified endophytes, isolated compounds and the standard anti-inflammatory drug (piroxicam). For prediction of the binding mode of the top-scoring constituents-targets complexes, the Schrödinger Maestro 11.8 package (LLC, New York, NY) was employed in the docking study.

Results

A total of 50 endophytic fungal isolates were separated from P. pruinosa leaves. Selection of six representative isolates was performed for further bioactivity screening based on their morphological characters, which were then identified as Stemphylium simmonsii MN401378, Stemphylium sp. MT084051, Alternaria infectoria MT573465, Alternaria alternata MZ066724, Alternaria alternata MN615420 and Fusarium equiseti MK968015. It could be observed that A. alternata MN615420 extract was the most potent anti-inflammatory candidate with a significant downregulation of TNF-α. Moreover, six secondary metabolites, alternariol monomethyl ether (1), 3’-hydroxyalternariol monomethyl ether (2), alternariol (3), α-acetylorcinol (4), tenuazonic acid (5) and allo-tenuazonic acid (6) were isolated from the most potent candidate (A. alternata MN615420). Among the tested isolated compounds, 3’-hydroxyalternariol monomethyl ether showed the highest anti-inflammatory potential with the most considerable reductions in the level of INF-γ and IL-1β. Meanwhile, alternariol monomethyl ether was the most potent TNF-α inhibitor. The energy values for the protein (IL-1β, TNF-α and INF-γ)–ligand interaction for the best conformation of the isolated compounds were estimated using molecular docking analysis.

Conclusions

The results obtained suggested alternariol derivatives may serve as naturally occurring potent anti-inflammatory candidates. This study opens new avenues for the design and development of innovative anti-inflammatory drugs that specifically target INF-γ, IL-1β and INF-γ.
Fitness-for-purpose of the CanMEDS competencies for workplace-based assessment in General Practitioner’s Training: a Delphi study
Authors: Andreou Vasiliki , Peters Sanne , Eggermont Jan , Embo Mieke , Michels Nele R. , Schoenmakers Birgitte
Published: April 2023

Background

In view of the exponential use of the CanMEDS framework along with the lack of rigorous evidence about its applicability in workplace-based medical trainings, further exploring is necessary before accepting the framework as accurate and reliable competency outcomes for postgraduate medical trainings. Therefore, this study investigated whether the CanMEDS key competencies could be used, first, as outcome measures for assessing trainees’ competence in the workplace, and second, as consistent outcome measures across different training settings and phases in a postgraduate General Practitioner’s (GP) Training.

Methods

In a three-round web-based Delphi study, a panel of experts (n = 25–43) was asked to rate on a 5-point Likert scale whether the CanMEDS key competencies were feasible for workplace-based assessment, and whether they could be consistently assessed across different training settings and phases. Comments on each CanMEDS key competency were encouraged. Descriptive statistics of the ratings were calculated, while content analysis was used to analyse panellists’ comments.

Results

Out of twenty-seven CanMEDS key competencies, consensus was not reached on six competencies for feasibility of assessment in the workplace, and on eleven for consistency of assessment across training settings and phases. Regarding feasibility, three out of four key competencies under the role “Leader”, one out of two competencies under the role “Health Advocate”, one out of four competencies under the role “Scholar”, and one out of four competencies under the role “Professional” were deemed as not feasible for assessment in a workplace setting. Regarding consistency, consensus was not achieved for one out of five competencies under “Medical Expert”, two out of five competencies under “Communicator”,one out of three competencies under “Collaborator”, one out of two under “Health Advocate”, one out of four competencies under “Scholar”, one out of four competencies under “Professional”. No competency under the role “Leader” was deemed to be consistently assessed across training settings and phases.

Conclusions

The findings indicate a mismatch between the initial intent of the CanMEDS framework and its applicability in the context of workplace-based assessment. Although the CanMEDS framework could offer starting points, further contextualization of the framework is required before implementing in workplace-based postgraduate medical trainings.
A structural equation modelling analysis: interprofessional team collaboration, organizational career management, and post competency of community nurses
Authors: Ma Li , Wang Xinwei , Zou Shiyue , Lin Min , Qiu Shi , Li Weimin
Published: April 2023

Background

With the advent of an ageing society and an increase in the prevalence of chronic diseases, the role of primary health care has become increasingly important and reliant on multidisciplinary collaboration. As members of this interprofessional cooperative team, community nurses play a dominant role. Thus, the post competencies of community nurses study deserve our attention. In addition, organizational career management can affect nurses in some ways. This study aims to examine the current situation and relationship among interprofessional team collaboration, organizational career management and post-competency of community nurses.

Methods

A survey was conducted among 530 nurses in 28 community medical institutions from November 2021 to April 2022 in Chengdu, Sichuan Province, China. Descriptive analysis was used for analysis, and a structural equation model was used to hypothesize and verify the model. A total of 88.2% of respondents met the inclusion criteria and did not meet the exclusion criteria. The main reason nurses gave for not participating was that they were too busy.

Results

Among the competencies on the questionnaire, ensuring quality and helping roles scored the lowest. The teaching-coaching and diagnostic functions played a mediating role. Nurses with greater seniority and those who were transferred to administrative departments had lower scores, and the difference was statistically significant (p < 0.05). In the structural equation model, CFI = 0.992 and RMSEA = 0.049, which shows that the model fit well, suggesting that organizational career management had no statistically significant effect on post competency (β = -0.006, p = 0.932) but that interprofessional team collaboration had a statistically significant effect on post competency (β = 1.146, p < 0.001) and organizational career management had a statistically significant effect on interprofessional team collaboration (β = 0.684, p < 0.001).

Conclusions

Attention should be given to the improvement of community nurses' post competency in ensuring quality and performing helping, teaching-coaching, and diagnostic roles. Moreover, researchers should focus on the decline in community nurses' abilities, particularly for those with greater seniority or in administrative roles. The structural equation model shows that interprofessional team collaboration is a complete intermediary between organizational career management and post competency.
Downregulation of circ-YES1 suppresses NSCLC migration and proliferation through the miR-142-3p–HMGB1 axis
Authors: Jin Mingming , Wang Yan , Zhou Dawei , Liu Wanchao , Han Ruodong , Chi Yongbin
Published: April 2023

Background

Circular RNAs (circRNAs) are a new family of abundant regulatory RNAs with roles in various types of cancer. While the hsa_circ_0046701 (circ-YES1) function in non-small cell lung cancer (NSCLC) is unclear.

Methods

Circ-YES1 expression in normal pulmonary epithelial and NSCLC cells was examined. The small interfering RNA for circ-YES1 was prepared, cell proliferation and migration were assessed. Tumorigenesis in nude mice was assayed to validate the role of circ-YES1. Bioinformatics analyses and luciferase reporter assays were utilized to identify downstream targets of circ-YES1.

Results

Compared to normal pulmonary epithelial cells, the circ-YES1 expression increased in NSCLC cells, and cell proliferation and migration were suppressed after circ-YES1 knockdown. Both high mobility group protein B1 (HMGB1) and miR-142-3p were found to be downstream targets of circ-YES1, and miR-142-3p inhibition and HMGB1 overexpression reversed the effects of circ-YES1 knockdown on cell proliferation and migration. Similarly, HMGB1 overexpression reversed the miR-142-3p overexpression effects on these two processes. The imaging experiment results revealed that circ-YES1 knockdown impeded tumor development and metastasis in a nude mouse xenograft model.

Conclusion

Taken together, our results show that circ-YES1 promotes tumor development through the miR-142-3p–HMGB1 axis and support the development of circ-YES1 probability as a new therapeutic NSCLC target.
Relationship between triglyceride-glucose index and aminotransferase among Royal Thai Army personnel 2017–2021: a serial cross-sectional study
Authors: Lertsakulbunlue Sethapong , Mungthin Mathirut , Rangsin Ram , Kantiwong Anupong , Sakboonyarat Boonsub
Published: April 2023

Background

Insulin resistance (IR) is a major pathogenesis of nonalcoholic fatty liver disease (NAFLD). The triglyceride-glucose (TyG) index has recently gained popularity to assess IR and NAFLD due to its simplicity and low cost. The aim of the current study was to evaluate the relationship between the TyG index and aminotransferase.

Methods

A serial cross-sectional study was conducted among 232,235 Royal Thai Army (RTA) personnel aged 35–60 years from 2017–2021. Elevated aminotransferase was defined as ≥ 40 U/L and ≥ 35 U/L among males and females, respectively. A linear regression analysis between the TyG index and log-transformed aminotransferase was performed. High- and low-TyG index groups were divided according to Youden’s index cut point for predicting elevated aminotransferase. Multivariable logistic analysis was also utilized to investigate the association between the TyG index and elevated aminotransferase.

Results

The TyG index revealed a dose‒response relationship with log-transformed aminotransferase in both sexes and all age groups. The TyG index was positively associated with the prevalence of elevated aminotransferases. In comparison with the first TyG quartile (< 8.37), participants in the fourth quartile (> 9.23) had a higher chance for elevated ALT (AOR: 2.81, 95% CI: 2.71–2.90 for males and AOR: 4.01, 95% CI: 3.50–4.60 for females, P < 0.001 for both). In the fourth TyG quartile, the prevalence of elevated ALT was 47.8% and 40.2% in the participants aged 35–44 and male participants, respectively.

Conclusion

A high TyG index is a novel risk factor for elevated aminotransferase among RTA personnel. Those with a high TyG index should be screened for elevated aminotransferase, particularly males aged 35–44 years.
Efficacy of granulocyte colony-stimulating factor for infertility undergoing IVF: a systematic review and meta-analysis
Authors: Fu Lu-lu , Xu Ying , Yan Jing , Zhang Xue-ying , Li Dan-dan , Zheng Lian-wen
Published: April 2023

Objective

This study aimed to evaluate the effectiveness of granulocyte colony-stimulating factor (G-CSF) for infertility and recurrent spontaneous abortion.

Methods

Existing research was searched in PubMed, Embase and Cochrane Library till Dec 2021. Randomized control trials (RCTs) that compared G-CSF administration with the control group in infertility women undergoing IVF were included. The primary outcomes included clinical pregnancy rate; the secondary outcomes included live birth rate, abortion ratebiochemical pregnancy rate, embryo implantation rate, as well as endometrial thickness.

Result(s)

20 RCTs were included in this study. G-CSF increased the clinical pregnancy rate (RR = 1.85; 95% CI: 1.07, 3.18) and the endometrial thickness (MD = 2.25; 95% CI: 1.58,2.92;) in patients with thin endometrium undergoing IVF. G-CSF increased the biochemical pregnancy rate (RR = 2.12; 95% CI: 1.54, 2.93), the embryo implantation rate (RR = 2.51; 95% CI: 1.82, 3.47) and the clinical pregnancy rate (RR = 1.93; 95% CI: 1.63, 2.29) in patients with a history of repeated implantation failure undergoing IVF. No differences were found in pregnancy outcomes of general IVF patients.

Conclusions

Granulocyte colony-stimulating factor is likely to be a potential option for infertility women undergoing IVF with thin endometrium or recurrent implantation failure .

Trial registration

Retrospectively registered (The PROSPERO registration number: CRD42022360161).
Early death after palliative radiation treatment: 30-, 35- and 40-day mortality data and statistically robust predictors
Authors: Nieder Carsten , Stanisavljevic Luka , Mannsåker Bård , Haukland Ellinor C.
Published: April 2023

Background

This study analyzed mortality after radiotherapy for bone metastases (287 courses). Endpoints such as treatment in the last month of life and death within 30, 35 and 40 days from start of radiotherapy were evaluated.

Methods

Different baseline parameters including but not limited to blood test results and patterns of metastases were assessed for association with early death. After univariate analyses, multi-nominal logistic regression was employed.

Results

Of 287 treatment courses, 42 (15%) took place in the last month of life. Mortality from start of radiotherapy was 13% (30-day), 15% (35-day) and 18% (40-day), respectively. We identified three significant predictors of 30-day mortality (performance status (≤ 50, 60–70, 80–100), weight loss of at least 10% within 6 months (yes/no), pleural effusion (present/absent)) and employed these to construct a predictive model with 5 strata and mortality rates of 0–75%. All predictors of 30-day mortality were also associated with both, 35- and 40-day mortality.

Conclusion

Early death was not limited to the first 30 days after start of radiotherapy. For different cut-off points, similar predictive factors emerged. A model based on three robust predictors was developed.
Predicting deterioration of patients with early sepsis at the emergency department using continuous heart rate variability analysis: a model-based approach
Authors: van Wijk Raymond J. , Quinten Vincent M. , van Rossum Mathilde C. , Bouma Hjalmar R. , ter Maaten Jan C.
Published: April 2023

Background

Sepsis is a life-threatening disease with an in-hospital mortality rate of approximately 20%. Physicians at the emergency department (ED) have to estimate the risk of deterioration in the coming hours or days and decide whether the patient should be admitted to the general ward, ICU or can be discharged. Current risk stratification tools are based on measurements of vital parameters at a single timepoint. Here, we performed a time, frequency, and trend analysis on continuous electrocardiograms (ECG) at the ED to try and predict deterioration of septic patients.

Methods

Patients were connected to a mobile bedside monitor that continuously recorded ECG waveforms from triage at the ED up to 48 h. Patients were post-hoc stratified into three groups depending on the development of organ dysfunction: no organ dysfunction, stable organ dysfunction or progressive organ dysfunction (i.e., deterioration). Patients with de novo organ dysfunction and those admitted to the ICU or died were also stratified to the group of progressive organ dysfunction. Heart rate variability (HRV) features over time were compared between the three groups.

Results

In total 171 unique ED visits with suspected sepsis were included between January 2017 and December 2018. HRV features were calculated over 5-min time windows and summarized into 3-h intervals for analysis. For each interval, the mean and slope of each feature was calculated. Of all analyzed features, the average of the NN-interval, ultra-low frequency, very low frequency, low frequency and total power were different between the groups at multiple points in time.

Conclusions

We showed that continuous ECG recordings can be automatically analyzed and used to extract HRV features associated with clinical deterioration in sepsis. The predictive accuracy of our current model based on HRV features derived from the ECG only shows the potential of HRV measurements at the ED. Unlike other risk stratification tools employing multiple vital parameters this does not require manual calculation of the score and can be used on continuous data over time.

Trial registration The protocol of this study is published by Quinten et al., 2017.
Plasma β2-microglobulin and cerebrospinal fluid biomarkers of Alzheimer’s disease pathology in cognitively intact older adults: the CABLE study
Authors: Huang Yi-Ming , Ma Ya-Hui , Gao Pei-Yang , Wang Zhi-Bo , Huang Liang-Yu , Hou Jia-Hui , Tan Lan , Yu Jin-Tai
Published: April 2023

Background

Previous studies have suggested a correlation between elevated levels of β2-microglobulin (B2M) and cognitive impairment. However, the existing evidence is insufficient to establish a conclusive relationship. This study aims to analyze the link of plasma B2M to cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers and cognition.

Methods

To track the dynamics of plasma B2M in preclinical AD, 846 cognitively healthy individuals in the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) cohort were divided into four groups (suspected non-AD pathology [SNAP], 2, 1, 0) according to the NIA-AA criteria. Multiple linear regression models were employed to examine the plasma B2M’s relationship with cognitive and CSF AD biomarkers. Causal mediation analysis was conducted through 10,000 bootstrapped iterations to explore the mediating effect of AD pathology on cognition.

Results

We found that the levels of plasma B2M were increased in stages 1 (P = 0.0007) and 2 (P < 0.0001), in contrast to stage 0. In total participants, higher levels of B2M were associated with worse cognitive performance (P = 0.006 for MMSE; P = 0.012 for MoCA). Moreover, a higher level of B2M was associated with decreases in Aβ1–42 (P < 0.001) and Aβ1–42/Aβ1–40 (P = 0.015) as well as increases in T-tau/Aβ1–42 (P < 0.001) and P-tau/Aβ1–42 (P < 0.001). The subgroup analysis found B2M correlated with Aβ1–42 in non-APOE ε4 individuals (P < 0.001) but not in APOE ε4 carriers. Additionally, the link between B2M and cognition was partially mediated by Aβ pathology (percentage: 8.6 to 19.3%), whereas tau pathology did not mediate this effect.

Conclusions

This study demonstrated the association of plasma B2M with CSF AD biomarkers as well as a possible important role of Aβ pathology in the association between B2M and cognitive impairment, particularly in cognitively normal individuals. The results indicated that B2M could be a potential biomarker for preclinical AD and might have varied functions throughout various stages of preclinical AD progression.
CT appearances and classification of hepatic epithelioid hemangioendothelioma
Authors: Tan Haidong , Zhou Ruiquan , Yu Hongwei , Teng Feng , Si Shuang , Liu Liguo , Yang Shiwei , Han Dongdong , Liu Xiaolei
Published: April 2023

Background

Hepatic epithelioid hemangioendothelioma (HEH) is extremely rare, and CT features have never been analyzed in a large group of patients.

Methods

A retrospective study was designed to review the contrast-enhanced CT images of HEH patients. Intrahepatic lesions were categorized into three types: nodular, locally coalescent (coalescent lesion contained in one segment) or diffusely coalescent (coalescent lesion occupied more than one segment). CT features were compared among lesions of different sizes and patients with different lesion types.

Results

A total of 93 HEH patients were included in this study, and 740 lesions were analyzed. The results of per-lesion analysis showed that medium lesions (2–5 cm) had the highest rate of lollipop sign (16.8%) and target-like enhancement (43.1%), while lesions in large group (> 5 cm) had the highest rate of capsular retraction (38.8%) and vascular invasion (38.8%). The differences on enhancement pattern and the rates of lollipop sign and capsular retraction were significant among lesions of different sizes (p < 0.001, respectively). The results of per-patient analysis showed that patients in locally coalescent group had the highest rates of lollipop sign (74.3%) and target sign (94.3%). All patients in diffusely coalescent group had capsular retraction and vascular invasion. CT appearances of capsular retraction, lollipop sign, target sign and vascular invasion differed significantly among patients with different lesion types (p < 0.001, p = 0.005, p = 0.006 and p < 0.001, respectively).

Conclusion

CT features variated among HEH patients with different lesion types, and radiological appearances of HEH should be classified into nodular type, locally coalescent type and diffusely coalescent type.
Development and validation of a glioma-associated mesenchymal stem cell-related gene prognostic index for predicting prognosis and guiding individualized therapy in glioma
Authors: Peng Zesheng , Wu Yuxi , Wang Jiajing , Gu Sujie , Wang Yihao , Xue Bingzhou , Fu Peng , Xiang Wei
Published: April 2023

Background

Recent studies have demonstrated that glioma-associated mesenchymal stem cells (GA-MSCs) are implicated in the regulation of glioma malignant progression. However, the prognostic value of GA-MSCs has not been comprehensively explored in glioma.

Methods

We extracted GA-MSCs from glioma tissues, established intracranial xenograft models in nude mice, and obtained GA-MSC-related genes (GA-MSCRGs) by using microarrays. The transcriptome data and clinical information of glioma patients were obtained from the CGGA and TCGA databases. We screened 8 prognostic GA-MSCRGs to construct a prognostic index by using the multivariate Cox regression method. The validity of the GA-MSCRGPI was verified in the training (CGGA693) and validation (TCGA and CGGA325) cohorts. The expression patterns of these 8 GA-MSCRGs were validated in 78 glioma tissue specimens by using a qRT‒PCR assay.

Results

GA-MSCs were successfully isolated from glioma tissues. Based on intracranial xenograft models and transcriptome microarray screening, 8 genes (MCM7, CDK6, ORC1, CCL20, TNFRSF12A, POLA1, TRAF1 and TIAM1) were selected for the construction of a GA-MSC-related gene prognostic index (GA-MSCRGPI). In both the training and validation cohorts, high GA-MSCRGPI patients showed an inferior survival outcome compared with low GA-MSCRGPI patients. A nomogram was established based on independent prognostic indicators (age, WHO grade and GA-MSCRGPI) and exhibited a strong forecasting ability for overall survival (OS). Moreover, we found that the GA-MSCRGPI could evaluate the prognosis of glioma patients undergoing chemoradiotherapy. The high GA-MSCRGPI group exhibited higher immune, stromal and ESTIMATE scores; lower tumor purity; higher infiltration of Tregs and M2-type macrophages; fewer activated NK cells; and higher expression of immune checkpoints. Tumor Immune Dysfunction and Exclusion (TIDE) showed that the high GA-MSCRGPI group had more responders to ICI therapy. The results of the genetic mutation profile and tumor mutation burden (TMB) in different GA-MSCRGPI subgroups further supplement GA-MSCRGPI-related mechanisms. Finally, the expression patterns of 8 selected GA-MSCRGs in GA-MSCRGPI were correlated with glioma WHO grades to a certain extent.

Conclusion

The constructed GA-MSCRGPI could predict prognosis and guide individualized therapy in glioma patients.
COVID-19 patient and personal safety – lessons learnt for pandemic preparedness and the way to the next normal
Authors: Füszl Astrid , Ebner Julia , Van den Nest Miriam , Bouvier-Azula Lukas , Diab-El Schahawi Magda , Presterl Elisabeth
Published: April 2023

Background

The COVID-19 pandemic has profoundly challenged societies and healthcare systems in particular. To prevent the spread of SARS-CoV-2, infection prevention and control (IPC) strategies had to be developed on the local, national and international level. The aim of this study is to provide details of the COVID-19 experience at the Vienna General Hospital (VGH) in the context of the national and international COVID-19 response for learning and improvement.

Methods

This is a retrospective report, outlining the evolution of IPC measures and challenges encountered at the health facility (VGH), the national (Austria) and global level between February 2020 and October 2022.

Results

The IPC strategy at the VGH has been continuously adapted to changes in the epidemiological setting, new legal directives and Austrian by-laws. The current strategy, nationally and internationally, focuses on endemicity rather than maximum transmission risk reduction. For the VGH, this has recently resulted in an increase in COVID-19 clusters. To protect our particularly vulnerable patients, many COVID-19 precautions have been maintained. Barriers to adequate IPC implementation at the VGH and other hospitals include a lack of sufficient isolation options and non-adherence with universal face mask regulations. Globally, misinformation on COVID-19 hampered an effective response.

Conclusions

This retrospective analysis of the COVID-19 response at the VGH and international reports underline the need for pandemic preparedness, readiness and response by improving future hospital design and infrastructure, conducting regular trainings for protective attire and increasing health literacy as now recently published in a concise document by WHO.
Effects of regorafenib on the mononuclear/phagocyte system and how these contribute to the inhibition of colorectal tumors in mice
Authors: Grünewald Sylvia , Stecklum Maria , Rizzo Manuel , Rathjens Jonathan , Fiebig Lukas , Zopf Dieter
Published: April 2023

Background

Regorafenib was previously shown to reduce tumor-associated macrophages and potently inhibit colony-stimulating factor 1 receptor (CSF1R), also known as CD115, in biochemical assays. The CSF1R signaling pathway is essential in the biology of the mononuclear/phagocyte system, which can promote the development of cancer.

Methods

A deeper investigation of regorafenib’s effects on CSF1R signaling was performed using preclinical in vitro and in vivo studies with syngeneic CT26 and MC38 mouse models of colorectal cancer. Peripheral blood and tumor tissue were analyzed mechanistically by flow cytometry using antibodies against CD115/CSF1R and F4/80 and by ELISA for chemokine (C–C motif) ligand 2 (CCL2) levels. These read-outs were correlated with drug levels for the detection of pharmacokinetic/pharmacodynamic relationships.

Results

Potent inhibition of CSF1R by regorafenib and its metabolites M-2, M-4, and M-5 was confirmed in vitro in RAW264.7 macrophages. The dose-dependent growth inhibition of subcutaneous CT26 tumors by regorafenib was associated with a significant reduction in both the number of CD115hi monocytes in peripheral blood and the number of selective subpopulations of intratumoral F4/80hi tumor-associated macrophages. CCL2 levels were not affected by regorafenib in blood but increased in tumor tissue, which may contribute to drug resistance and prevent complete tumor remission. An inverse relationship between regorafenib concentration and the number of CD115hi monocytes and CCL2 levels was observed in peripheral blood, supporting the mechanistic involvement of regorafenib.

Conclusions

These findings may be clinically useful in optimizing drug dosing using blood-based pharmacodynamic markers and in identifying resistance mechanisms and ways to overcome them by appropriate drug combinations.
Numerical Investigation of the Progressive Collapse of the Reinforced Concrete Wall-Frame Structures Considering the Soil–Structure Interaction
Authors: Ekrami Kakhki Seyed Ali , Kheyroddin Ali , Mortezaei Alireza
Published: April 2023

In this essay, the progressive collapse resistance of the reinforced concrete wall-frame structures was evaluated with and without considering the soil–structure interaction. The vulnerability of the frames against progressive collapse was investigated with the middle column removal scenario from the first story, based on the sensitivity index. To evaluate the effects of soil–structure interaction, the wall-frame structures along with the soil (hard soil) and foundation were simultaneously modeled in FLAC software and compared with the frames in Seismostruct software. The results showed that the sensitivity index decreased by considering the soil–structure interaction in the wall-frame structures. Afterward, a parametric study of the structures (foundation thickness) and substructures (soil types, soil densities, soil saturation conditions and soil layers) was performed. The results showed that with an increase in thickness of the foundation, the sensitivity index increased, and therefore, the condition of the structure would be more critical against progressive collapse. It was found that high groundwater levels in the subsoil can reduce its bearing capacity and lead to the damage to the structure. In addition, it was determined that by changing the substructure soil type from type 4 (Clay-MC) to type 1 (Rock), the use of layer 1 (SM) and layer 2 (SM-CL/ML (Very hard clay)-SM), and the soils with high density, the condition of the structures is better to prevent progressive collapse.
Self-regulation as a resource for coping with developmental challenges during middle childhood and adolescence: the prospective longitudinal PIERYOUTH-study
Authors: Warschburger P. , Gmeiner M. S. , Bondü R. , Klein A. M. , Busching R. , Elsner B.
Published: April 2023

Background

Self-regulation (SR) as the ability to regulate one’s own physical state, emotions, cognitions, and behavior, is considered to play a pivotal role in the concurrent and subsequent mental and physical health of an individual. Although SR skills encompass numerous sub-facets, previous research has often focused on only one or a few of these sub-facets, and only rarely on adolescence. Therefore, little is known about the development of the sub-facets, their interplay, and their specific contributions to future developmental outcomes, particularly in adolescence. To fill these research gaps, this study aims to prospectively examine (1) the development of SR and (2) their influence on adolescent-specific developmental outcomes in a large community sample.

Methods/design

Based on previously collected data from the Potsdam Intrapersonal Developmental Risk (PIER) study with three measurement points, the present prospective, longitudinal study aims to add a fourth measurement point (PIERYOUTH). We aim to retain at least 1074 participants now between 16 and 23 years of the initially 1657 participants (6–11 years of age at the first measurement point in 2012/2013; 52.2% female). The study will continue to follow a multi-method (questionnaires, physiological assessments, performance-based computer tasks), multi-facet (assessing various domains of SR), and multi-rater (self-, parent-, and teacher-report) approach. In addition, a broad range of adolescent-specific developmental outcomes is considered. In doing so, we will cover the development of SR and relevant outcomes over the period of 10 years. In addition, we intend to conduct a fifth measurement point (given prolonged funding) to investigate development up to young adulthood.

Discussion

With its broad and multimethodological approach, PIERYOUTHaims to contribute to a deeper understanding of the development and role of various SR sub-facets from middle childhood to adolescence. The large sample size and low drop-out rates in the first three measurements points form a sound database for our present prospective research.

Trial registrationGerman Clinical Trials Register, registration number DRKS00030847.
Effectiveness of clear aligners in achieving proclination and intrusion of incisors among Class II division 2 patients: a multivariate analysis
Authors: Yan Xinyu , Zhang Xiaoqi , Ren Linghuan , Yang Yi , Wang Qingxuan , Gao Yanzi , Jiang Qingsong , Jian Fan , Long Hu , Lai Wenli
Published: April 2023

Background

The predictability of incisor movement achieved by clear aligners among Class II division 2 patients is poorly understood. The aim of this retrospective study was to determine the effectiveness of clear aligners in proclining and intruding upper incisors and its influencing factors.

Methods

Eligible patients with Class II division 2 malocclusion were included. For clear aligner therapy, three types of incisor movements were designed: proclination, intrusion and labial movement. Pre-treatment and post-treatment dental models were superimposed. The differences between predicted and actual (DPA) tooth movement of incisors were analyzed. Univariate and multivariate linear regression were used to analyze the potential influencing factors.

Results

A total of 51 patients and their 173 upper incisors were included. Actual incisor proclination and intrusion were less than predicted ones (both P < 0.001), while actual labial movement was greater than predicted one (P < 0.001). Predictability of incisor proclination and intrusion was 69.8% and 53.3%, respectively. Multivariate linear regression revealed that DPA of proclination was significantly positively associated with predicted proclination (B = 0.174, P < 0.001), ipsilateral premolar extraction (B = 2.773, P < 0.001) and ipsilateral canine proclination (B = 1.811, P < 0.05), while negatively associated with molar distalization (B = − 2.085, P < 0.05). The DPA of intrusion was significantly positively correlated with predicted intrusion (B = 0.556, P < 0.001) while negatively associated with labial mini-implants (B = − 1.466, P < 0.001). The DPA of labial movement was significantly positively associated with predicted labial movement (B = 0.481, P < 0.001), while negatively correlated with molar distalization (B = − 1.004, P < 0.001), labial mini-implants (B = − 0.738, P < 0.001) and age (B = − 0.486, P < 0.05).

Conclusions

For Class II division 2 patients, predicted incisor proclination (69.8%) and intrusion (53.3%) are partially achieved with clear aligner therapy. Excessive labial movement (0.7 mm) of incisors may be achieved. Incisor movement is influenced by predicted movement amount, premolar extraction, canine proclination, molar distalization, mini-implants and age.
The Wakayama earthquake swarm in Japan
Authors: Nakajima Junichi
Published: April 2023

An earthquake swarm in the Wakayama prefecture, Japan, is known as the most active and persistent swarm, with > 95,000 earthquakes (M ≥ –1.3) occurring during the 2003–2020 period. However, no systematic studies have highlighted the source of this intriguing non-volcanic earthquake swarm to date. This study systematically investigates the temporal and spatial evolution of the Wakayama earthquake swarm and estimates the seismic velocity structure around the Kii peninsula, where we observe series of anomalous geophysical and geochemical signatures, such as high 3He/4He ratios, deep low-frequency earthquakes, and hot springs with high salinity and solute concentrations. We reveal that seismicity associated with the Wakayama earthquake swarm occurs almost evenly in both time and space, and that the majority of the earthquakes in the northern part of the swarm activity occur along well-defined planes that dip to the west at 30–45°. The seismic tomography results reveal that a northwestward-dipping low-velocity zone exists beneath the Wakayama swarm and the low-velocity zone is sandwiched by high-velocity anomalies in the continental crust interpreted as impermeable and rigid materials on both sides in the subduction direction. This unique tectonic setting controls a pathway of the upward migration of slab-derived fluids to the surface, with the high fluid concentration in the dipping low-velocity zone. Therefore, we infer that the location of the Wakayama swarm is controlled by deep crustal heterogeneities rather than by the major structures of geological accretionary complexes. This study suggests that the anomalous geophysical and geochemical signatures observed across the Kii peninsula are different manifestations of the frictional and hydrological processes during the upward migration of the slab-derived fluids. We further propose that the valley-shaped geometry of the Philippine Sea slab beneath the Kii peninsula is caused by the rigid materials in the continental crust.

Graphical Abstract
In vitro analysis and in vivo assessment of fracture complications associated with use of locking plate constructs for stabilization of caprine tibial segmental defects
Authors: Bowers Kristin M. , Wright Ellis M. , Terrones Lori D. , Sun Xiaocun , Rifkin Rebecca , Grzeskowiak Remi , Croy Elizabeth , Seddighi Reza , Kleine Stephanie , Hampton Chiara , Hecht Silke , Adair Henry S. , Anderson David E. , Mulon Pierre‐Yves
Published: April 2023

Purpose

Locking plate fixation of caprine tibial segmental defects is widely utilized for translational modeling of human osteopathology, and it is a useful research model in tissue engineering and orthopedic biomaterials research due to its inherent stability while maintaining unobstructed visualization of the gap defect and associated healing. However, research regarding surgical technique and long‐term complications associated with this fixation method are lacking. The goal of this study was to assess the effects of surgeon‐selected factors including locking plate length, plate positioning, and relative extent of tibial coverage on fixation failure, in the form of postoperative fracture.

Methods

In vitro, the effect of plate length was evaluated using single cycle compressive load to failure mechanical testing of locking plate fixations of caprine tibial gap defects. In vivo, effects of plate length, positioning, and relative tibial coverage were evaluated using data from a population of goats enrolled in ongoing orthopedic research which utilized locking plate fixation of 2 cm tibial diaphyseal segmental defects to evaluate bone healing over 3, 6, 9, and 12 months.

Results

In vitro, no significant differences in maximum compressive load or total strain were noted between fixations using 14 cm locking plates and 18 cm locking plates. In vivo, both plate length and tibial coverage ratio were significantly associated with postoperative fixation failure. The incidence of any cortical fracture in goats stabilized with a 14 cm plate was 57%, as compared with 3% in goats stabilized with an 18 cm plate. Craniocaudal and mediolateral angular positioning variables were not significantly associated with fixation failure. Decreasing distance between the gap defect and the proximal screw of the distal bone segment was associated with increased incidence of fracture, suggesting an effect on proximodistal positioning on overall fixation stability.

Conclusions

This study emphasizes the differences between in vitro modeling and in vivo application of surgical fixation methods, and, based on the in vivo results, maximization of plate‐to‐tibia coverage is recommended when using locking plate fixation of the goat tibial segmental defect as a model in orthopedic research.
Risk factors of postoperative cerebral hyperperfusion syndrome and its relationship with clinical prognosis in adult patients with moyamoya disease
Authors: Shi Zhiyong , Wu Lingyun , Wang Yi , Zhang Huasheng , Yang Yongbo , Hang Chunhua
Published: April 2023

Background

To investigate the incidence, risk factors, and clinical prognosis of cerebral hyperperfusion syndrome (CHS) after superficial temporal artery-middle cerebral artery anastomosis combined with encephalo-duro-arterio-synangiosis (STA-MCA/EDAS) in adult patients with moyamoya disease (MMD).

Methods

The clinical data of 160 adult patients with MMD treated by STA-MCA/EDAS from January 2016 to January 2017 were retrospectively analyzed. According to CHS diagnosis, MMD patients were divided into CHS and non-CHS group. Univariate and multivariate analysis of risk factors and Kaplan-Meier curve of stroke-free survival for CHS were performed.

Results

A total of 12 patients (7.5%) developed postoperative CHS, of which 4 patients (2.5%) presented with cerebral hemorrhage. Univariate and multivariate analysis showed moyamoya vessel on the surgical hemisphere (OR = 3.04, 95% CI = 1.02–9.03, P = 0.046) and left operated hemisphere (OR = 5.16, 95% CI = 1.09–21.34, P = 0.041) were independent risk factors for CHS. The other variables, such as age, gender, presentation, hypertension, diabetes, smoking, mean mRS score on admission, modified Suzuki stage and pre-infarction stage on surgical hemisphere, and bypass patency, had no association with postoperative CHS (P > 0.05). At final follow-up with average 38 months, there were 18 out of 133 patients (13.5%, 4.91% per person year) presented with newly developed complications. There was no significant difference between newly developed complications, mean mRS scores, and Kaplan-Meier curve of stroke-free survival in patients with and without CHS (P > 0.05).

Conclusion

The concentration of moyamoya vessels and left operated hemisphere was independent risk factors for CHS, which could not affect the clinical prognosis if treated timely and properly. The current study offers a new perspective of moyamoya vessels and supporting data for choosing MMD candidates on cerebral revascularization.
High-resolution wildfire simulations reveal complexity of climate change impacts on projected burn probability for Southern California
Authors: Dye Alex W. , Gao Peng , Kim John B. , Lei Ting , Riley Karin L. , Yocom Larissa
Published: April 2023

Background

Wildfire is a major contemporary socio-ecological issue facing the people and natural resources of Southern California, and the prospect that a warming climate could lead to a higher probability of fire in the future is cause for concern. However, connecting climate change to projected burn probability is complex. While most models generally show temperature increasing in the future, changes in humidity and precipitation are less certain, and these changes interact to generate projections of future climates that are sometimes, but not always, more conducive to wildfire. We ran FSim, a stochastic, high-resolution spatial (270 m) and temporal (daily) fire spread model, with projected Energy Release Component (ERC) derived from multiple global climate models (GCMs) under RCP8.5 climate change scenario to explore the impact of a range of future climate trajectories on simulated burn probability and to quantify the uncertainty arising from multiple GCMs.

Results

We observed considerable uncertainty in the future direction of change for burn probability. Future changes were more certain in the Southern Coast region of California, where 75% of simulations projected an increase in burn probability. In the Central Coast region, five out of eight GCM-based simulations projected increased burn probability. Less than 1% of the total burnable study area had unanimous agreement on the projected direction of change. Simulated changes in burn probability were directly correlated to annual projections of changes in ERC, but were also affected by the seasonality of ERC change, as well as interactions between humidity, precipitation, and temperature.

Conclusions

The observed variability offers insights into why, and under what climate conditions, burn probability may increase or decrease in the future. Our study is novel in its examination of a wide range of potential future burn probability projections for Southern California using a regional application of a high-resolution stochastic fire spread model, and the complexity that we demonstrated for Southern California suggests that simple correlations of increasing fire with increasing temperature are likely underestimating the range of plausible future fire scenarios.
Accessory pathways in monozygotic twins with different clinical phenotypes: a case report
Authors: Marzak Halim , Fitouchi Simon , Cardi Thomas , Kanso Mohamad , Schatz Alexandre , Jesel Laurence
Published: April 2023

Background

The atrioventricular reentrant tachycardia (AVRT) is the most common tachycardia associated with accessory pathways (APs). Although sporadic Wolff-Parkinson-White (WPW) syndrome has been well-described, AP occurrence in identical twins with WPW syndrome remains rarely reported.

Case presentation

We report a case of 14-year-old monozygotic twin brothers referred for an electrophysiology (EP) study. Twin A presented with recurrent symptomatic narrow complex tachycardia after exercise, noted for 3 years. His 12-lead surface electrocardiogram (ECG) did not show ventricular pre-excitation. However, an orthodromic AVRT utilizing a concealed right posteroseptal AP was found and successfully ablated. AVRT did not recur 12 months after the procedure. Twin B was asymptomatic. During his medical examination for firefighter volunteerism, his 12-lead ECG showed a spontaneous ventricular pre-excitation. EP study revealed a short anterograde right midseptal AP, which was then successfully eliminated by catheter ablation. His 12-lead ECG showed no ventricular pre-excitation recurrence 12 months after the procedure.

Conclusions

These identical twin brothers had a right-side AP in almost the same place but showed completely different phenotypes. This case clearly illustrates the difficulty in understanding genetic contribution in the origin of atrioventricular APs. Environmental exposure could play a role in their clinical presentations and AP electrophysiological properties.