bluuebunny/crossref_metadata_2025 huggingface dataset:
Perspectives of family medicine residents in Riyadh on leadership training: a cross-sectional study
Authors: Alluhaymid Yousef , Alalwan Abdulaziz , Alruwaitea Abdulmajeed
Published: March 2023

Background

Medical educators in academia have faced challenges incorporating leadership training into curricula while minimizing redundancy and assuring value and relevance for all learners. This study aims to assess the status of leadership training as perceived by family medicine residents in Riyadh to advise the development of a formal leadership training curriculum.

Method

The research is cross-sectional and quantitative. Participants were asked via an electronic questionnaire about their leadership attitudes, perceived degree of training in various leadership domains, and where they could find additional training.

Results

The survey was completed by 270 family medicine residents in Riyadh. Residents rated the importance of physician leadership in their communities as high (6 out of 7 on a Likert scale). In contrast, agreement with the statement 'I am a leader' obtained the lowest grade (4.4 of 7 on a Likert scale). Overall, most of the residents participating in the study (50% or more) voiced a desire for more training in all leadership domains. Over 50% of residents indicated that leadership electives or selective lectures, workshops, or seminars as well as WADAs (Weekly Academic Day Activities), leadership mentors or coaches teaching junior learners (with training), and leadership courses could be incorporated into the curriculum to foster leadership skills.

Conclusion

Residents were enthusiastic about family physicians being leaders, aligning with the current educational philosophy but requiring formal training. They also indicated areas where leadership training might be improved and developed in the current curriculum. This poll's results could be used to help residents build leadership skills by incorporating them into a formal leadership curriculum.
The pre-analytical process management status and influencing factors of laboratory test before prescribing antimicrobial in developing country
Authors: Zheng Feiyang , Wang Kang , Wang Qianning , Yu Tiantian , Zhang Xinping
Published: March 2023

Introduction

The results of laboratory testing are crucial basis for clinicians to prescribe antimicrobial. Laboratory testing is a highly complex process, and increasing evidence suggests that errors and obstacles in the pre-analytical process (PP) will affect reasonable antimicrobial use. However, PP was an easily neglected link in hospital infection management and the current situation of it and the influencing factors of management are not clear.

Methods

A cross-sectional survey was conducted in the department of clinical, specimen collection, transportation, and inspection in 109 secondary and tertiary hospitals in Central China. The rate of antimicrobial susceptibility test request (AST) and related indexes of above departments were calculated to describe the situation. Management characteristics (frequency of training etc.) were described as proportions and fractional probit regression analysis was used to determine the influencing factors.

Results

The average rate of non restricted-use antimicrobial was 63%, the restricted-use was 86%, the special-use was 95%. The zero obstacle rate of specimen collection was 27.3%, of specimen transportation was 19.4% and of inspection feedback was 61.7%. There was a difference between the secondary and tertiary hospitals on non restricted-use (X2 = 22.968, P < 0.001); restricted-use (X2 = 29.466, P < 0.001); special-use (X2 = 27.317, P < 0.001). Taking non restricted-use as an example, training (OR = 0.312, 95%CI: 0.148,0.429), low-frequency appraisal (OR = 0.153, 95%CI: 0.082,0.224), guidance (OR = 0.32, 95%CI: 0.237,0.403) and information technology (OR = 0.104, 95%CI: 0.009,0.199) were positive factors.

Conclusions

There were substantial differences in the rate of AST request in clinical department between secondary and tertiary hospitals. The zero obstacle rate in collection, transportation and inspection department were still low. In most departments, training and performance appraisal were positive factors, guidance and information technology were positive supporting factors.
Weighted gene co-expression network analysis revealed T cell differentiation associated with the age-related phenotypes in COVID-19 patients
Authors: Lin Yao , Li Yueqi , Chen Hubin , Meng Jun , Li Jingyi , Chu Jiemei , Zheng Ruili , Wang Hailong , Pan Peijiang , Su Jinming , Jiang Junjun , Ye Li , Liang Hao , An Sanqi
Published: March 2023

The risk of severe condition caused by Corona Virus Disease 2019 (COVID-19) increases with age. However, the underlying mechanisms have not been clearly understood. The dataset GSE157103 was used to perform weighted gene co-expression network analysis on 100 COVID-19 patients in our analysis. Through weighted gene co-expression network analysis, we identified a key module which was significantly related with age. This age-related module could predict Intensive Care Unit status and mechanical-ventilation usage, and enriched with positive regulation of T cell receptor signaling pathway biological progress. Moreover, 10 hub genes were identified as crucial gene of the age-related module. Protein–protein interaction network and transcription factors-gene interactions were established. Lastly, independent data sets and RT-qPCR were used to validate the key module and hub genes. Our conclusion revealed that key genes were associated with the age-related phenotypes in COVID-19 patients, and it would be beneficial for clinical doctors to develop reasonable therapeutic strategies in elderly COVID-19 patients.
HbA1c-based rather than fasting plasma glucose-based definitions of prediabetes identifies high-risk patients with angiographic coronary intermediate lesions: a prospective cohort study
Authors: Song Chenxi , Yuan Sheng , Cui Kongyong , Cai Zhongxing , Zhang Rui , He Jining , Qiao Zheng , Bian Xiaohui , Wu Shaoyu , Wang Haoyu , Shi Boqun , Lin Zhangyu , Fu Rui , Wang Chunyue , Liu Qianqian , Jia Lei , Dong Qiuting , Dou Kefei
Published: March 2023

Background

Prediabetes is common and associated with poor prognosis in patients with acute coronary syndrome and those undergoing revascularization. However, the impact of prediabetes on prognosis in patients with coronary intermediate lesions remains unclear. The objective of the current study is to explore the impact of prediabetes and compare the prognostic value of the different definitions of prediabetes in patients with coronary intermediate lesions.

Methods

A total of 1532 patients attending Fuwai hospital (Beijing, China), with intermediate angiographic coronary lesions, not undergoing revascularization, were followed-up from 2013 to 2021. Patients were classified as normal glucose tolerance (NGT), prediabetes and diabetes according to various definitions based on HbA1c or admission fasting plasma glucose (FPG). The primary endpoint was defined as major adverse cardiovascular events (MACE), the composite endpoint of all-cause death, non-fatal myocardial infarction and repeated revascularization therapy. Multivariate cox regression model was used to explore the association between categories of abnormal glucose category and MACE risk.

Results

The proportion of patients defined as prediabetes ranged from 3.92% to 47.06% depending on the definition used. A total of 197 MACE occurred during a median follow-up time of 6.1 years. Multivariate cox analysis showed that prediabetes according to the International Expert Committee (IEC) guideline (6.0 ≤ HbA1c < 6.5%) was associated with increased risk of MACE compared with NGT (hazard ratio [HR]: 1.705, 95% confidence interval [CI] 1.143–2.543) and after confounding adjustment (HR: 1.513, 95%CI 1.005–2.277). Consistently, the best cut-off point of glycated haemoglobin (HbA1c) identified based on the Youden’s index was also 6%. Restricted cubic spline analysis delineated a linear positive relationship between baseline HbA1c and MACE risk. Globally, FPG or FPG-based definition of prediabetes was not associated with patients’ outcome.

Conclusions

In this cohort of patients with intermediate coronary lesions not undergoing revascularization therapy, prediabetes based on the IEC-HbA1c definition was associated with increased MACE risk compared with NGT, and may assist in identifying high-risk patients who can benefit from early lifestyle intervention.
Time-dependent effect of GLP-1 receptor agonists on cardiovascular benefits: a real-world study
Authors: Piccini Sara , Favacchio Giuseppe , Panico Cristina , Morenghi Emanuela , Folli Franco , Mazziotti Gherardo , Lania Andrea Gerardo , Mirani Marco
Published: March 2023

Background

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown cardiovascular benefits in cardiovascular outcome trials in type 2 diabetes mellitus. However, the most convincing evidence was obtained in subjects with established cardiovascular (CV) disease. We analyzed the determinants of GLP-1 RA-mediated CV protection in a real-world population of persons with type 2 diabetes with and without a history of CV events with long-term follow-up.

Methods

Retrospective cohort study of 550 individuals with type 2 diabetes (395 in primary CV prevention, 155 in secondary CV prevention), followed at a single center after the first prescription of a GLP-1 RA between 2009 and 2019. CV and metabolic outcomes were assessed.

Results

Median duration of follow-up was 5.0 years (0.25–10.8) in primary prevention and 3.6 years (0–10.3) in secondary prevention, with a median duration of treatment of 3.2 years (0–10.8) and 2.5 years (0–10.3) respectively. In the multivariable Cox regression model considering GLP-1 RA treatment as a time-dependent covariate, in the primary prevention group, changes in BMI and glycated hemoglobin did not have an impact on MACE risk, while age at the time of GLP-1 initiation (HR 1.08, 95% CI 1.03–1.14, p = 0.001) and GLP-1 RA cessation by time (HR 3.40, 95% CI 1.82–6.32, p < 0.001) increased the risk of MACE. Regarding the secondary prevention group, only GLP-1 RA cessation by time (HR 2.71, 95% CI 1.46–5.01, p = 0.002) increased the risk of MACE. With respect to those who withdrew treatment, subjects who continued the GLP-1 RA had significantly greater weight loss and lower glycated hemoglobin levels during follow-up.

Conclusions

In this real-world type 2 diabetes population, discontinuation of GLP-1 RA treatment was associated to a higher risk of major cardiovascular events, in both subjects with and without a history of CV events.
The five continuum of care criteria that should accompany rectal artesunate interventions: lessons learned from an implementation study in Malawi
Authors: Oliff Monique S. , Muniina Pamela , Babigumira Kenneth , Phuka John , Rietveld Hans , Sande John , Nsona Humphreys , Lugand Maud M.
Published: March 2023

Background

Rectal artesunate (RAS) is a World Health Organization (WHO) recommended intervention that can save lives of children 6 years and younger suffering from severe malaria and living in remote areas. Access to RAS and a referral system that ensures continuity of care remains a challenge in low resource countries, raising concerns around the value of this intervention. The objective of this study was to inform RAS programming, using practical tools to enhance severe malaria continuum of care when encountered at community level.

Methods

A single country two-arm-controlled study was conducted in Malawi, where pre-referral interventions are provided by community health workers (CHWs). The study populations consisted of 9 and 14 village health clinics (VHCs) respectively, including all households with children 5 years and younger. CHWs in the intervention arm were trained using a field-tested toolkit and the community had access to information, education, and communication (IEC) mounted throughout the zone. The community in the control arm had access to routine care only. Both study arms were provided with a dedicated referral booklet for danger signs, as a standard of care.

Results

The study identified five continuum of care criteria (5 CoC Framework) to reinforce RAS programming: (1) care transitions emerged as to be dependent on a strong cue to action and proximity to an operational VHC with a resident CHWs; (2) consistency of supplies assured the population of the VHC’s functionality for severe danger signs management; (3) comprehensiveness care ensured correct assessment and dosing; (4) connectivity of care between all tiers using the referral slip was feasible and perceived positively by caregivers and CHWs and (5) communication between providers from different points of care. Compliance was high throughout but optimized when administered by a sensitized CHW. Over 93% experienced a rapid improvement in the status of their child post RAS.

Conclusion

RAS cannot operate within a vacuum. The impact of this lifesaving intervention can be easily lost, unless administered as part of a system-based approach. Taken together, the 5CC Framework, identified in this study, provides a structure for future RAS practice guidelines.

Trial registration number and date of registration PACTR201906720882512- June 20, 2019.
Unleashing the potential of combining FGFR inhibitor and immune checkpoint blockade for FGF/FGFR signaling in tumor microenvironment
Authors: Ruan Ruiwen , Li Li , Li Xuan , Huang Chunye , Zhang Zhanmin , Zhong Hongguang , Zeng Shaocheng , Shi Qianqian , Xia Yang , Zeng Qinru , Wen Qin , Chen Jingyi , Dai Xiaofeng , Xiong Jianping , Xiang Xiaojun , Lei Wan , Deng Jun
Published: March 2023

Background

Fibroblast growth factors (FGFs) and their receptors (FGFRs) play a crucial role in cell fate and angiogenesis, with dysregulation of the signaling axis driving tumorigenesis. Therefore, many studies have targeted FGF/FGFR signaling for cancer therapy and several FGFR inhibitors have promising results in different tumors but treatment efficiency may still be improved. The clinical use of immune checkpoint blockade (ICB) has resulted in sustained remission for patients.

Main

Although there is limited data linking FGFR inhibitors and immunotherapy, preclinical research suggest that FGF/FGFR signaling is involved in regulating the tumor microenvironment (TME) including immune cells, vasculogenesis, and epithelial-mesenchymal transition (EMT). This raises the possibility that ICB in combination with FGFR-tyrosine kinase inhibitors (FGFR-TKIs) may be feasible for treatment option for patients with dysregulated FGF/FGFR signaling.

Conclusion

Here, we review the role of FGF/FGFR signaling in TME regulation and the potential mechanisms of FGFR-TKI in combination with ICB. In addition, we review clinical data surrounding ICB alone or in combination with FGFR-TKI for the treatment of FGFR-dysregulated tumors, highlighting that FGFR inhibitors may sensitize the response to ICB by impacting various stages of the “cancer-immune cycle”.
Machine-learning screening of luminogens with aggregation-induced emission characteristics for fluorescence imaging
Authors: Zhang Yibin , Fan Miaozhuang , Xu Zhourui , Jiang Yihang , Ding Huijun , Li Zhengzheng , Shu Kaixin , Zhao Mingyan , Feng Gang , Yong Ken-Tye , Dong Biqin , Zhu Wei , Xu Gaixia
Published: March 2023

Due to the excellent biocompatible physicochemical performance, luminogens with aggregation-induced emission (AIEgens) characteristics have played a significant role in biomedical fluorescence imaging recently. However, screening AIEgens for special applications takes a lot of time and efforts by using conventional chemical synthesis route. Fortunately, artificial intelligence techniques that could predict the properties of AIEgen molecules would be helpful and valuable for novel AIEgens design and synthesis. In this work, we applied machine learning (ML) techniques to screen AIEgens with expected excitation and emission wavelength for biomedical deep fluorescence imaging. First, a database of various AIEgens collected from the literature was established. Then, by extracting key features using molecular descriptors and training various state-of-the-art ML models, a multi-modal molecular descriptors strategy has been proposed to extract the structure-property relationships of AIEgens and predict molecular absorption and emission wavelength peaks. Compared to the first principles calculations, the proposed strategy provided greater accuracy at a lower computational cost. Finally, three newly predicted AIEgens with desired absorption and emission wavelength peaks were synthesized successfully and applied for cellular fluorescence imaging and deep penetration imaging. All the results were consistent successfully with our expectations, which demonstrated the above ML has a great potential for screening AIEgens with suitable wavelengths, which could boost the design and development of novel organic fluorescent materials.
Identification of prognostic and therapeutic biomarkers in type 2 papillary renal cell carcinoma
Authors: Wang Yue , Tian Xi , Zhu Shu-Xuan , Xu Wen-Hao , Anwaier Aihetaimujiang , Su Jia-Qi , Gan Hua-Lei , Qu Yuan-Yuan , Zhao Jian-Yuan , Zhang Hai-Liang , Ye Ding-Wei
Published: March 2023

Background

Papillary renal cell carcinoma (PRCC) can be divided into type 1 (PRCC1) and type 2 (PRCC2) and PRCC2 share a more invasive phenotype and worse prognosis. This study aims to identify potential prognostic and therapeutic biomarkers in PRCC2.

Methods

A cohort from The Cancer Genome Atlas and two datasets from Gene Expression Omnibus were examined. Common differentially expressed genes (DEGs) were screened and potential biomarkers were explored by using Kaplan–Meier method and cox regression analysis. Functional enrichment analysis was utilized to evaluate the potential biological functions. Tumor infiltrating immune cells were estimated by CIBERSORT algorithm. Ninety-two PRCC2 samples from Fudan University Shanghai Cancer Center were obtained, and immunostaining was performed to validate prognostic and therapeutic significance of the potential biomarker.

Results

PRCC2 has worse overall survival and shares distinct molecular characteristics from PRCC1. There was significant higher expression level of Targeting protein for Xklp2 (TPX2) in PRCC2 compared with normal tissues. Higher expression level of TPX2 was significantly associated with worse overall survival in PRCC2 and kinesin family genes expression were found significantly elevated in high risk PRCC2. Abundance of tumor infiltrating M1 macrophage was significantly higher in PRCC2 and it was also associated with worse overall survival. In the FUSCC cohort, higher TPX2 expression was significantly correlated with worse overall and progression-free survival. Retrospective analysis indicated that mTOR inhibitor (everolimus) had greater efficacy in the high-risk group than in the low-risk group (overall response rate: 28.6% vs. 16.7%) and that everolimus had greater efficacy than sunitinib in the high-risk group (overall response rate: 28.6% vs. 20%).

Conclusions

TPX2 was a prognostic and therapeutic biomarker in PRCC2. Higher abundance of tumor infiltrating M1 macrophage was significantly associated with worse overall survival in PRCC2. mTOR inhibitors may have good efficacy in patients with high-risk PRCC2.
Reference values for wrist-worn accelerometer physical activity metrics in England children and adolescents
Authors: Fairclough Stuart J. , Rowlands Alex V. , del Pozo Cruz Borja , Crotti Matteo , Foweather Lawrence , Graves Lee E. F. , Hurter Liezel , Jones Owen , MacDonald Mhairi , McCann Deborah A. , Miller Caitlin , Noonan Robert J. , Owen Michael B. , Rudd James R. , Taylor Sarah L. , Tyler Richard , Boddy Lynne M.
Published: March 2023

Background

Over the last decade use of raw acceleration metrics to assess physical activity has increased. Metrics such as Euclidean Norm Minus One (ENMO), and Mean Amplitude Deviation (MAD) can be used to generate metrics which describe physical activity volume (average acceleration), intensity distribution (intensity gradient), and intensity of the most active periods (MX metrics) of the day. Presently, relatively little comparative data for these metrics exists in youth. To address this need, this study presents age- and sex-specific reference percentile values in England youth and compares physical activity volume and intensity profiles by age and sex.

Methods

Wrist-worn accelerometer data from 10 studies involving youth aged 5 to 15 y were pooled. Weekday and weekend waking hours were first calculated for youth in school Years (Y) 1&2, Y4&5, Y6&7, and Y8&9 to determine waking hours durations by age-groups and day types. A valid waking hours day was defined as accelerometer wear for ≥ 600 min·d−1 and participants with ≥ 3 valid weekdays and ≥ 1 valid weekend day were included. Mean ENMO- and MAD-generated average acceleration, intensity gradient, and MX metrics were calculated and summarised as weighted week averages. Sex-specific smoothed percentile curves were generated for each metric using Generalized Additive Models for Location Scale and Shape. Linear mixed models examined age and sex differences.

Results

The analytical sample included 1250 participants. Physical activity peaked between ages 6.5–10.5 y, depending on metric. For all metrics the highest activity levels occurred in less active participants (3rd-50th percentile) and girls, 0.5 to 1.5 y earlier than more active peers, and boys, respectively. Irrespective of metric, boys were more active than girls (p < .001) and physical activity was lowest in the Y8&9 group, particularly when compared to the Y1&2 group (p < .001).

Conclusions

Percentile reference values for average acceleration, intensity gradient, and MX metrics have utility in describing age- and sex-specific values for physical activity volume and intensity in youth. There is a need to generate nationally-representative wrist-acceleration population-referenced norms for these metrics to further facilitate health-related physical activity research and promotion.
Mesenchymal stromal cells promote the drug resistance of gastrointestinal stromal tumors by activating the PI3K-AKT pathway via TGF-β2
Authors: Zhao Yu , Weng Zuyi , Zhou Xuan , Xu Zhi , Cao Bei , Wang Bin , Li Juan
Published: March 2023

Background

Gastrointestinal stromal tumors (GISTs) are the prevailing sarcomas of the gastrointestinal tract. Tyrosine kinase inhibitors (TKIs) therapy, exemplified by Imatinib mesylate (IM), constitutes the established adjuvant therapy for GISTs. Nevertheless, post-treatment resistance poses a challenge that all patients must confront. The presence of tumor heterogeneity and secondary mutation mechanisms fail to account for some instances of acquired drug resistance. Certain investigations suggest a strong association between tumor drug resistance and mesenchymal stromal cells (MSC) in the tumor microenvironment, but the underlying mechanism remains obscure. Scarce research has explored the connection between GIST drug resistance and the tumor microenvironment, as well as the corresponding mechanism.

Methods

Immunofluorescence and fluorescence-activated cell sorting (FACS) methodologies were employed to detect the presence of MSC in GIST samples. The investigation encompassed the examination of MSC migration towards tumor tissue and the impact of MSC on the survival of GIST cells under IM treatment. Through ELISA, western blotting, and flow cytometry analyses, it was confirmed that Transforming Growth Factor Beta 2 (TGF-β2) triggers the activation of the PI3K-AKT pathway by MSC, thereby facilitating drug resistance in GIST.

Results

Our findings revealed a positive correlation between a high proportion of MSC and both GIST resistance and a poor prognosis. In vitro studies demonstrated the ability of MSC to migrate towards GIST. Additionally, MSC were observed to secrete TGF-β2, consequently activating the PI3K-AKT pathway and augmenting GIST resistance.

Conclusions

Our investigation has revealed that MSC within GISTs possess the capacity to augment drug resistance, thereby highlighting their novel mechanism and offering a promising target for intervention in GIST therapy.
Mitochondrial ROS driven by NOX4 upregulation promotes hepatocellular carcinoma cell survival after incomplete radiofrequency ablation by inducing of mitophagy via Nrf2/PINK1
Authors: Peng Chao , Li Xi , Ao Feng , Li Ting , Guo Jingpei , Liu Junfeng , Zhang Xiaoting , Gu Jinyan , Mao Junjie , Zhou Bin
Published: March 2023

Background

The recurrence of hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) remains a major clinical problem. Cells that survive the sublethal heat stress that is induced by incomplete RFA are the main source of HCC relapse. Heat stress has long been reported to increase intracellular reactive oxygen species (ROS) generation. Although ROS can induce apoptosis, a pro-survival effect of ROS has also been demonstrated. However, the role of ROS in HCC cells exposed to sublethal heat stress remains unclear.

Methods

HepG2 and HuH7 cells were used for this experiment. Insufficient RFA was performed in cells and in a xenograft model. ROS and antioxidant levels were measured. Apoptosis was analyed by Annexin-V/PI staining and flow cytometry. Protein expression was measured using western blotting. Colocalization of lysosomes and mitochondria was analyzed to assess mitophagy. Corresponding activators or inhibitors were applied to verify the function of specific objectives.

Results

Here,we showed that sublethal heat stress induced a ROS burst, which caused acute oxidative stress. This ROS burst was generated by mitochondria, and it was initiated by upregulated NOX4 expression in the mitochondria.n-acetylcysteine (NAC) decreased HCC cell survival under sublethal heat stress conditions in vivo and in vitro. NOX4 triggers the production of mitochondrial ROS (mtROS), and NOX4 inhibitors or siNOX4 also decreased HCC cell survival under sublethal heat stress conditions in vitro. Increased mtROS trigger PINK1-dependent mitophagy to eliminate the mitochondria that are damaged by sublethal heat stress and to protect cells from apoptosis. Nrf2 expression was elevated in response to this ROS burst and mediated the ROS burst-induced increase in PINK1 expression after sublethal heat stress.

Conclusion

These data confirmed that the ROS burst that occurs after iRFA exerted a pro-survival effect. NOX4 increased the generation of ROS by mitochondria. This short-term ROS burst induced PINK1-dependent mitophagy to eliminate damaged mitochondria by increasing Nrf2 expression.
Microglial aryl hydrocarbon receptor enhances phagocytic function via SYK and promotes remyelination in the cuprizone mouse model of demyelination
Authors: Wang Yumeng , Sun Jingxian , Zhu Keying , Wang Danjie , Zhao Xiaoqiang , Zhang Hongyu , Wu Shuai , Wang Yanqing , Wang Jun
Published: March 2023

Multiple sclerosis (MS) is an inflammatory-mediated demyelinating disease of the central nervous system (CNS). Although studies have demonstrated that microglia facilitate remyelination in demyelinating diseases, the underlying mechanisms are still not fully characterized. We found that aryl hydrocarbon receptor (AhR), an environment sensor, was upregulated within the corpus callosum in the cuprizone model of CNS demyelination, and upregulated AhR was mainly confined to microglia. Deletion of AhR in adult microglia inhibited efficient remyelination. Transcriptome analysis using RNA-seq revealed that AhR-deficient microglia displayed impaired gene expression signatures associated with lysosome and phagocytotic pathways. Furthermore, AhR-deficient microglia showed impaired clearance of myelin debris and defected phagocytic capacity. Further investigation of target genes of AhR revealed that spleen tyrosine kinase (SYK) is the downstream effector of AhR and mediated the phagocytic capacity of microglia. Additionally, AhR deficiency in microglia aggravated CNS inflammation during demyelination. Altogether, our study highlights an essential role for AhR in microglial phagocytic function and suggests the therapeutic potential of AhR in demyelinating diseases.

Graphical Abstract
Provision and experience of care among women with hypertension in pregnancy: a multi-center qualitative study in Ghana
Authors: Adu-Bonsaffoh Kwame , Tamma Evelyn , Nwameme Adanna , Dako-Gyeke Phyllis , Srofenyoh Emmanuel , Ansah Evelyn K. , Grobbee Diederick E. , Franx Arie , Browne Joyce L.
Published: March 2023

Background

Hypertensive disorders of pregnancy (HDP) remain a leading global health problem with complex clinical presentations and potentially grim birth outcomes for both mother and fetus. Improvement in the quality of maternal care provision and positive women’s experiences are indispensable measures to reduce maternal and perinatal adverse outcomes.

Objective

To explore the perspectives and lived experiences of healthcare provision among women with HDP and the associated challenges.

Methods

A multi-center qualitative study using in-depth interviews (IDIs) and focus group discussions (FGDs) was conducted in five major referral hospitals in the Greater Accra Region of Ghana between June 2018 and March 2019. Women between 26 and 34 weeks’ gestation with confirmed HDP who received maternity care services were eligible to participate. Thematic content analysis was performed using the inductive analytic framework approach.

Results

Fifty IDIs and three FGDs (with 22 participants) were conducted. Most women were between 20 and 30 years, Akans (ethnicity), married/cohabiting, self-employed and secondary school graduates. Women reported mixed (positive and negative) experiences of maternal care. Positive experiences reported include receiving optimal quality of care, satisfaction with care and good counselling and reassurance from the health professionals. Negative experiences of care comprised ineffective provider–client communication, inappropriate attitudes by the health professionals and disrespectful treatment including verbal and physical abuse. Major health system factors influencing women’s experiences of care included lack of logistics, substandard professionalism, inefficient national health insurance system and unexplained delays at health facilities. Patient-related factors that influenced provision of care enumerated were financial limitations, chronic psychosocial stress and inadequate awareness about HDP.

Conclusion

Women with HDP reported both positive and negative experiences of care stemming from the healthcare system, health providers and individual factors. Given the importance of positive women’s experiences and respectful maternal care, dedicated multidisciplinary women-centered care is recommended to optimize the care for pregnant women with HDP.
Effects of collagen membrane on bone level and periodontal status of adjacent tooth after third molar surgery: a randomized controlled trial
Authors: Kilinc Adnan , Ataol Mert
Published: March 2023

Background

The periodontal status and distal bone level of the adjacent second molar can be negatively affected by the surgical extraction of an impacted lower third molar. Absorbable materials have some benefits, including enhancing primary wound coverage and promoting wound healing through isolation, clotting, wound stabilization and haemostasis. This study set out to compare primary and secondary healing and collagen-membrane-based primary healing after surgical removal of partially erupted impacted third molars (3Ms), evaluating the distal alveolar bone level (ABL) and periodontal status of the adjacent second molars (2Ms).

Methods

Patients who met the inclusion criteria were randomized into three groups: secondary healing (n = 28), primary healing (n = 27) and membrane-based primary healing (n = 29). Digital panoramic radiographs were obtained preoperatively (T1) and three months postoperatively (T2). The distances between the cemento-enamel junctions and the alveolar bone crests on the distal aspects of the adjacent 2Ms were measured using calibrated radiograph measurement software. The pocket depth and plaque index measurements were performed preoperatively and three months postoperatively. The periodontal plaque index (PPI) scores were registered on the distal aspects of the 2Ms, and the mean values were used.

Results

Three of the applied healing types positively affected periodontal pocket depth (PPD) and periodontal index values (p < 0.05). In terms of the ABL of the adjacent 2Ms, primary healing (p < 0.05) and membrane-based primary healing (p < 0.05) had superior results to secondary healing.

Conclusion

Membrane use is promising for the distal bone gain and periodontal status of the adjacent 2M.

Trial registration

This clinical study was registered by the Australian New Zealand Clinical Trials Registry, with the trial number ACTRN12618001551280.
The effect of hyperbaric oxygen therapy on the clinical outcomes of necrotizing soft tissue infections: a systematic review and meta-analysis
Authors: Huang Chengzi , Zhong Yilian , Yue Chaochi , He Bin , Li Yaling , Li Jun
Published: March 2023

Background

To determine the efficacy of hyperbaric oxygen therapy (HBO) in the treatment of necrotizing soft tissue infections (NSTI), we conducted a meta-analysis of the available evidence.

Methods

Data sources were PubMed, Embase, Web of Science, Cochrane Library, and reference lists. The study included observational trials that compared HBO with non-HBO, or standard care. The primary outcome was the mortality rate. Secondary outcomes were the number of debridement, amputation rate and complication rate. Relative risks or standardized mean differences with 95% confidence intervals were calculated for dichotomous and continuous outcomes, respectively.

Results

A total of retrospective cohort and case-control studies were included, including 49,152 patients, 1448 who received HBO and 47,704 in control. The mortality rate in the HBO group was significantly lower than that in the non-HBO group [RR = 0.522, 95% CI (0.403, 0.677), p < 0.05]. However, the number of debridements performed in the HBO group was higher than in the non-HBO group [SMD = 0.611, 95% CI (0.012, 1.211), p < 0.05]. There was no significant difference in amputation rates between the two groups [RR = 0.836, 95% CI (0.619, 1.129), p > 0.05]. In terms of complications, the incidence of MODS was lower in the HBO group than in the non-HBO group [RR = 0.205, 95% CI (0.164, 0.256), p < 0.05]. There was no significant difference in the incidence of other complications, such as sepsis, shock, myocardial infarction, pulmonary embolism, and pneumonia, between the two groups (p > 0.05).

Conclusion

The current evidence suggests that the use of HBO in the treatment of NSTI can significantly reduce the mortality rates and the incidence rates of complications. However, due to the retrospective nature of the studies, the evidence is weak, and further research is needed to establish its efficacy. It is also important to note that HBO is not available in all hospitals, and its use should be carefully considered based on the patient's individual circumstances. Additionally, it is still worthwhile to stress the significance of promptly evaluating surgical risks to prevent missing the optimal treatment time.
Clinical study of vacuum phenomenon in closed pelvic fracture
Authors: Yang Rui-Feng , Huang Shu-Ming , Wu Quan-Zhou , Ye Fang , Lan Shu-Hua
Published: March 2023

Background

This study aimed to examine the prevalence and clinical findings of the vacuum phenomenon (VP) in closed pelvic fractures.

Methods

We retrospectively reviewed 352 patients with closed pelvic fractures who presented to our institution from January 2017 to December 2020. Pelvic fractures were diagnosed by plain radiography and computed tomography (CT). The default “bone window” was used for inspection in the cross section. Electronic medical records were consulted by two orthopedic physicians to obtain patient information. The VP of pelvic fracture, fracture classification, injury mechanism, and image data were evaluated, and the demographic parameter data were statistically analyzed. The follow-up time was 12–18 months.

Results

Among them, 169 were males and 183 were females with ages ranging from 3 to 100 years, with an average of 49.6 ± 19.3 years. VP in pelvic fractures was detected by CT in 109 (31%) of the 352 patients with pelvic fractures. Patients were divided into the high-energy trauma group (278 cases) and fragility fractures of the pelvis (FFP) group (74 cases) according to the injury mechanism. In the high-energy trauma group, 227 cases were treated surgically and 201 cases had bony healing. The healing time was 9.8 ± 5.3 weeks. In the FFP group, 54 cases were treated surgically and 49 cases had bone healing. The healing time was 9.3 ± 3.8 weeks. Fractures progressed in nine patients. VP was mostly located in the sacroiliac joint in our study.

Conclusions

The incidence of VP in pelvic fractures is statistically high and is affected by many factors, such as examination technique, joint position, population composition, etc. Therefore, the VP is not a reliable sign of pelvic injury. Clinically, we need to determine the nature of VP in conjunction with gas patterns, laboratory tests, history, and physical examination.
Fibrin clot and Leukocyte-rich platelet-rich fibrin show similar release kinetics and amount of growth factors: a pilot study
Authors: Nakanishi Yuta , Matsushita Takehiko , Nagai Kanto , Araki Daisuke , Hoshino Yuichi , Kuroda Ryosuke
Published: March 2023

Background

In knee arthroscopic surgery, fibrin clot (FC) and leukocyte-rich platelet-rich fibrin (L-PRF) may be used in augmentation for meniscal repair. Studies have investigated growth factors released from FC and L-PRF; however, it is difficult to compare FC and L-PRF between different studies. Direct comparison of growth factors that may support meniscal healing released from FC and L-PRF may be beneficial in deciding whether to use FC or L-PRF. If no significant difference is seen, the surgeon may decide to use FC which is easier to prepare compared to L-PRF. The purpose of this pilot study is to investigate the release amount and pattern of basic fibroblast growth factor (bFGF), platelet-derived growth factor AB (PDGF-AB), transforming growth factor β1 (TGF-β1), vascular endothelial growth factor (VEGF), and stromal cell-derived factor 1 (SDF-1) from FC and L-PRF.

Method

Twenty milliliters (ml) of whole blood was collected from each of the four volunteers. Ten milliliters of whole blood was allocated for preparation of FC and 10 ml for L-PRF. FC and L-PRF were separately placed in 5 ml of culture media. Five milliliters of the culture media was sampled and refilled at 15 min, 1 day, 3 days, 1 week and 2 weeks. The collected culture was used to quantify bFGF, PDGF-AB, TGF-β1, VEGF, and SDF-1 release by Enzyme-linked immune-sorbent assay (ELISA). Mann–Whitney U test was performed to assess significance of differences in amount of each growth factor released between FC and L-PRF. Significance was accepted at P value less than 0.05.

Results

At two weeks, the cumulative release of TGF-β1 was the highest among all the growth factors in both FC and L-PRF (FC:19,738.21 pg/ml, L-PRF: 16,229.79 pg/ml). PDGF-AB (FC: 2328 pg/ml, L-PRF 1513.57 pg/ml) had the second largest amount, followed by VEGF (FC: 702.06 pg/ml, L-PRF 595.99 pg/ml) and bFGF (FC: 23.48 pg/ml, L-PRF 18.2 pg/ml), which order was also common in both FC and L-PRF. No significant difference in final release amount and pattern was seen between FC and L-PRF.

Conclusion

The current pilot study showed that cumulative release amount and release pattern of PDGF-AB, VEGF, TGF-β1, and bFGF did not significantly differ between FC and L-PRF during the two weeks of observation.
Accuracies of various types of spinal robot in robot-assisted pedicle screw insertion: a Bayesian network meta-analysis
Authors: Xie Lin-Zhen , Wang Qi-Long , Zhang Qi , He Da , Tian Wei
Published: March 2023

Background

With the popularization of robot-assisted spinal surgeries, it is still uncertain whether robots with different designs could lead to different results in the accuracy of pedicle screw placement. This study aimed to compare the pedicle screw inserting accuracies among the spinal surgeries assisted by various types of robot and estimate the rank probability of each robot-assisted operative technique involved.

Methods

The electronic literature database of PubMed, Web of Science, EMBASE, CNKI, WANFANG and the Cochrane Library was searched in November 2021. The primary outcome was the Gertzbein–Robbins classification of pedicle screws inserted with various operative techniques. After the data extraction and direct meta-analysis process, a network model was established in the Bayesian framework and further analyses were carried out.

Results

Among all the 15 eligible RCTs, 4 types of robot device, namely Orthbot, Renaissance, SpineAssist and TiRobot, were included in this study. In the network meta-analysis, the Orthbot group (RR 0.27, 95% CI 0.13–0.58), the Renaissance group (RR 0.33, 95% CI 0.14–0.86), the SpineAssist group (RR 0.14, 95% CI 0.06–0.34) and the conventional surgery group (RR 0.21, 95% CI 0.13–0.31) were inferior to the TiRobot group in the proportion of grade A pedicle screws. Moreover, the results of rank probabilities revealed that in terms of accuracy, the highest-ranked robot was TiRobot, followed by Renaissance and Orthbot.

Conclusions

In general, current RCT evidence indicates that TiRobot has an advantage in the accuracy of the pedicle screw placement, while there is no significant difference among the Orthbot-assisted technique, the Renaissance-assisted technique, the conventional freehand technique, and the SpineAssist-assisted technique in accuracy.
Psychometric evaluation of the Indolent Systemic Mastocytosis Symptom Assessment Form (ISM-SAF©) and determination of a threshold score for moderate symptoms
Authors: Shields Alan L. , Taylor Fiona , Lamoureux Roger E. , Padilla Brad , Severson Kas , Green Tanya , Boral Anthony L. , Akin Cem , Siebenhaar Frank , Mar Brenton
Published: March 2023

Background

The Indolent Systemic Mastocytosis Symptom Assessment Form (ISM-SAF) (©Blueprint Medicines Corporation), a 12-item daily diary that assesses 11 signs and symptoms of indolent systemic mastocytosis (ISM) and smoldering systemic mastocytosis (SSM), was psychometrically evaluated among patients with ISM. Additionally, thresholds of the ISM-SAF total symptom score (TSS) to distinguish patients with moderate to severe symptoms from those with mild symptoms were evaluated.

Methods

The ISM-SAF was completed daily as an electronic diary in a prospective, observational study utilizing an online survey of patients with ISM in the United States. Descriptive statistics, psychometric analyses, and analyses to estimate ISM-SAF TSS clinical cutoff values were conducted.

Results

A total of 103 patients (81.6% female; mean age = 50.2 [± 12.6]) with a self-reported diagnosis of ISM or SSM (58 of whom also had a medically documented diagnosis) contributed to the analyses. Psychometric analysis supported the trustworthiness of the biweekly TSS, which was reliable (α > 0.8, ICC > 0.9), construct-valid, and able to distinguish among clinically distinct groups as specified by the Patient Global Impression of Severity, 12-item Short-Form Health Survey, and Mastocytosis Quality of Life Questionnaire (p < 0.01). A biweekly ISM-SAF TSS from 21 to 28 begins to distinguish the moderately to severely symptomatic ISM/SSM patients from mildly symptomatic patients.

Conclusion

The biweekly TSS of ISM-SAF was reliable, construct-valid, and able to distinguish among clinically distinct groups. A cut-off value of 28 is a conservative threshold that can be used for screening purposes in future clinical studies to identify patients with at least a moderate severity of ISM symptoms.
Recent advances in targeted therapies in acute myeloid leukemia
Authors: Bhansali Rahul S. , Pratz Keith W. , Lai Catherine
Published: March 2023

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. While survival for younger patients over the last several decades has improved nearly sixfold with the optimization of intensive induction chemotherapy and allogeneic stem cell transplantation (alloHSCT), this effect has been largely mitigated in older and less fit patients as well as those with adverse-risk disease characteristics. However, the last 10 years has been marked by major advances in the molecular profiling of AML characterized by a deeper understanding of disease pathobiology and therapeutic vulnerabilities. In this regard, the classification of AML subtypes has recently evolved from a morphologic to a molecular and genetic basis, reflected by recent updates from the World Health Organization and the new International Consensus Classification system. After years of stagnation in new drug approvals for AML, there has been a rapid expansion of the armamentarium against this disease since 2017. Low-intensity induction therapy with hypomethylating agents and venetoclax has substantially improved outcomes, including in those previously considered to have a poor prognosis. Furthermore, targeted oral therapies against driver mutations in AML have been added to the repertoire. But with an accelerated increase in treatment options, several questions arise such as how to best sequence therapy, how to combine therapies, and if there is a role for maintenance therapy in those who achieve remission and cannot undergo alloHSCT. Moreover, certain subtypes of AML, such as those with TP53 mutations, still have dismal outcomes despite these recent advances, underscoring an ongoing unmet need and opportunity for translational advances. In this review, we will discuss recent updates in the classification and risk stratification of AML, explore the literature regarding low-intensity and novel oral combination therapies, and briefly highlight investigative agents currently in early clinical development for high-risk disease subtypes.
Rate of progressive healing with a carbon‐fiber orthosis in cases of partial union and nonunion after ankle arthrodesis using the Ilizarov external fixator
Authors: Cibura Charlotte , Lotzien Sebastian , Rosteius Thomas , Ull Christopher , Godolias Periklis , Schildhauer Thomas Armin , Königshausen Matthias
Published: March 2023

Background

The Ilizarov fixator is a popular device for treating arthrodesis of the ankle joint in complex situations. However, the therapy can fail, with nonunion or partial union that might not be load stable. There is the possibility of follow‐up surgery or extended wearing of the fixator. Full weight bearing with a carbon orthosis remains another treatment option, which has not yet been investigated.The aim of the study was to determine the rate of progress that can be obtained with a carbon orthosis in cases of partial union or nonunion after fixator removal.

Methods

In this retrospective observational study thirty‐three patients received a carbon orthosis after fixator removal due to nonunion or partial union. All patients were allowed to walk with the orthosis under full load. The consolidation rate was determined radiologically and compared with the imaging data obtained during the last follow‐up. In addition to demographic data, the Foot and Ankle Ability Measure and pain using a numeric rating scale were determined. Nine patients had to be excluded due to insufficient follow‐up, and finally n = 24 patients were included in the study.

Results

The average duration of fixator use was 21 weeks (range 15–40 weeks), and the total average follow‐up after removal of the fixator was 16 months (range 4‐ 56). For 14 (58.33%) patients, there was a further increase in consolidation with the orthosis after the fixator was removed.

Conclusion

The results show that if there is only partial union or nonunion, further consolidations can be achieved after the application of a carbon orthosis. In a difficult patient population, using an orthosis should therefore be attempted to avoid unnecessary revision operations.