bluuebunny/crossref_metadata_2025 huggingface dataset:
The pervasive association between political ideology and COVID-19 vaccine uptake in Brazil: an ecologic study
Authors: Seara-Morais Gabriel J. , Avelino-Silva Thiago J. , Couto Marcia , Avelino-Silva Vivian I.
Published: August 2023

Background

Despite the unequivocal benefits of vaccination, vaccine coverage has been falling in several countries in the past few years. Studies suggest that vaccine hesitancy is an increasingly significant phenomenon affecting adherence to vaccines. More recently, during the COVID-19 pandemic, political views have emerged as an additional influencing factor for vaccine hesitancy.

Methods

In this ecologic study, we used information from publicly available databases to investigate the association between political ideology, depicted by the percentage of votes for the right-wing candidate Jair Bolsonaro in the presidential elections of 2018 and 2022, and COVID-19 vaccination in Brazilian municipalities. The primary endpoint was the COVID-19 vaccination index, calculated as the number of COVID-19 vaccine doses administered up to September 2022 divided by the number of inhabitants in each municipality. The analysis was conducted using Pearson correlation coefficients and linear regression models adjusted for HDI, the percentage of male voters, the percentage of voters who were older than 50 years old, and the percentage of voters with a middle school education or less. In addition, we explored whether the effect of the percentage of Bolsonaro voters on the COVID-19 vaccination index was modified in different quartiles of HDI using an interaction term.

Results

Five thousand five hundred sixty-three Brazilian municipalities were included in the analysis. For both the 2018 and 2022 elections, the percentage of votes for Jair Bolsonaro was significantly and inversely associated with COVID-19 vaccine uptake after adjustment for the sociodemographic characteristics of the voters (change in mean vaccination index in 2018 for each 1% increase in Bolsonaro voters -0.11, 95% confidence interval [CI] -0.13 to -0.08, p < 0.001; change in mean vaccination index in 2022 for each 1% increase in Bolsonaro voters -0.09, 95% CI -0.11 to -0.07, p < 0.001). We also found a statistically significant interaction between the primary predictor of interest and HDI scores, with a more significantly detrimental effect of the right-wing political stance in municipalities in the lower HDI quartiles (interaction p < 0.001 for the first HDI quartile; p = 0.001 for the second HDI quartile).

Conclusion

Our findings suggest that political ideologies have influenced COVID-19 vaccine hesitancy in Brazilian municipalities, affecting communities inequitably. The politicization of vaccines is a new challenge for vaccine programs. Strategies to face these challenges should include joint efforts from governments and civil society for a common public health goal.
Mutual pathways between peer and own e-cigarette use among youth in the United States: a cross-lagged model
Authors: Cheng Hui G. , Lizhnyak Pavel N. , Richter Nadja
Published: August 2023

Background

Electronic cigarettes (e-cigarettes) have become the most common tobacco product used among adolescents in the United States (US). Prior research has shown that peer e-cigarette use was associated with increased risk of own e-cigarette use. Nonetheless, there is little empirical evidence on the directionality of these associations—if peer use predicts own use (peer influence) or if own use predicts peer use (peer selection).

Methods

We estimated the association between peer and own e-cigarette use among US adolescents 12–17 years of age. We used the cross-lagged model to investigate the mutual relationship between peer and own e-cigarette use over time using data from a population-based longitudinal study, Population Assessment of Tobacco and Health. Stratified analyses were conducted by sex and age subgroups.

Results

Results from a cross-lagged model showed a statistically significant predicting path leading from peer use at the prior time point to own use at the following time point, but not vice versa.

Conclusions

We found strong relationships between peer e-cigarette use and own e-cigarette use at within-individual levels. Peer influence paths were more robust than peer selection paths for e-cigarette use. Incorporating peers into prevention and intervention programs may help enhance these strategies.
The association between admission serum albumin and preoperative deep venous thrombosis in geriatrics hip fracture: a retrospective study of 1819 patients with age ≥ 65 years
Authors: Wu Yi-Lun , Zhang Dan , Zhang Kai-Yuan , Yan Ting , Qiang Wen-Si , Zhang Ting , Zhang Bin-Fei
Published: August 2023

Objective

This study evaluated the association between serum albumin levels and preoperative deep vein thrombosis (DVT) in geriatric hip fractures.

Methods

Older adult patients with hip fractures were screened between January 2015 and September 2019. The demographic and clinical characteristics of the patients were collected. Multivariate binary logistic regression and generalized additive model were used to identify the linear and nonlinear association between albumin levels and preoperative DVT. Analyses were performed using EmpowerStats and the R software.

Results

A total of 1819 patients were included in this study. The average age was 79.37 ± 6.88 years. There were 550 males and 1269 females. The preoperative albumin was 38.19 ± 4.07 g/L. There were 580 (31.89%) preoperative DVTs. Multivariate binary logistic regression showed that albumin level was associated with preoperative DVT (odds ratio [OR] = 0.94, 95% confidence interval [CI]: 0.91–0.97, P = 0.0002) after adjusting for confounding factors. The fully adjusted model showed a DVT risk decrease of 6% when albumin concentration increased by one g/L after controlling for confounding factors. In addition, the trend test and propensity score matching also showed a stable linear correlation between albumin level and preoperative DVT.

Conclusion

Serum albumin is associated with preoperative DVT in geriatric patients with hip fractures, and it could be considered a predictor for the risk of DVT.

Registration ID

ChiCTR2200057323.
Dynamic cord compression induced by proximal junctional failure and loose pedicle screws after thoracolumbar fusion surgery: a case report
Authors: Kozaki Takahiro , Kozaki Takuhei , Nagata Keiji , Tsutsui Shunji , Noda Yusuke , An Howard S , Yamada Hiroshi
Published: August 2023

Background

One of the common mechanical complications following spinal fusion surgery is proximal junctional failure (PJF). The incidence of neurological deficit associated with PJF has been poorly described in the literature. Here, we report a case in which numbness in the lower extremities was recognized as the first symptom, but the discrepancy in the imaging findings made PJF difficult to diagnose.

Methods

A 71-year-old female underwent corrective fusion surgery. Three weeks later, she complained of persistent right leg numbness. Standing X-ray showed the back-out of the pedicle screws (PSs) in the upper instrumented vertebra (UIV), but there was no obvious evidence of cord compression on computed tomography (CT), which caused the delay of diagnosis. Five weeks later, magnetic resonance image (MRI) did not show cord compression on an axial view, but there were signal changes in the spinal cord.

Results

The first reason for the delayed diagnosis was the lack of awareness that leg numbness could occur as the first symptom of PJF. The second problem was the lack of evidence for spinal cord compression in various imaging tests. Loosened PSs were dislocated on standing, but were back to their original position on supine position. In our case, these contradictory images led to a delay in diagnosis.

Conclusion

Loosened PSs caused dynamic cord compression due to repeated deviation and reduction. Supine and standing radiographs may be an important tool in the diagnosis of PJF induced by dynamic cord compression.
A novel technique for avoidance of sternotomy, diaphragmic incision and cardiopulmonary bypass during cavoatrial tumor thrombectomy for renal cell carcinoma with intraatrial tumor thrombus: a case series at a single center
Authors: He Wei , Cong Zixiang , Liu Yaqing , Yao Zhongshun , Cheng Fajuan , Zhang Yiming , Niu Zhihong
Published: August 2023

Background

Radical nephrectomy with thrombectomy in patients with renal cell carcinoma (RCC) and level IV thrombus extending to the right atrium (RA) offers improved survival. However, this procedure is associated with significant perioperative morbidity and mortality. In this report, we describe a novel milking technique for patients with RA tumor thrombus using abdominal access, which does not require diaphragmic incision, sternotomy, right atriotomy, or cardiopulmonary bypass (CPB).

Methods

Between January 2019 and January 2022, four patients underwent resection of renal cell carcinoma extending into RA by a milking technique developed to avoid diaphragmic incision, sternotomy, or CPB. Patient characteristics, perioperative data, pathological features, and survival were evaluated.

Results

Complete resection was successful through pure transabdominal access without diaphragmic incision, sternotomy, or CPB in all patients.

Conclusion

We conclude that radical nephrectomy and thrombectomy in optimized cases with renal cell carcinoma extending into RA can be safely and effectively performed without diaphragmic incision, sternotomy, or CPB, avoiding serious perioperative complications while providing acceptable oncological outcomes.
Investigating the association between educational attainment and allostatic load with risk of cancer mortality among African American women
Authors: Li Cynthia , Andrzejak Sydney Elizabeth , Jones Samantha R. , Williams Brittany Marie , Moore Justin Xavier
Published: August 2023

Background

African American (AA) women navigate the world with multiple intersecting marginalized identities. Accordingly, AA women have higher cumulative stress burden or allostatic load (AL) compared to other women. Studies suggest that AA women with a college degree or higher have lower AL than AA women with less than a high school diploma. We examined the joint effect of educational attainment and AL status with long-term risk of cancer mortality, and whether education moderated the association between AL and cancer mortality.

Methods

We performed a retrospective analysis among 4,677 AA women within the National Health and Nutrition Examination Survey (NHANES) from 1988 to 2010 with follow-up data through December 31, 2019. We fit weighted Cox proportional hazards models to estimate adjusted hazard ratios (aHRs) of cancer death between educational attainment/AL (adjusted for age, income, and smoking status).

Results

AA women with less than a high school diploma living with high AL had nearly a 3-fold increased risk (unadjusted HR: 2.98; 95%C CI: 1.24–7.15) of cancer death compared to AA college graduates living with low AL. However, after adjusting for age, this effect attenuated (age-adjusted HR: 1.11; 95% CI: 0.45–2.74). AA women with high AL had 2.3-fold increased risk of cancer death (fully adjusted HR: 2.26; 95% CI: 1.10–4.57) when compared to AA with low AL, specifically among women with high school diploma or equivalent and without history of cancer.

Conclusions

Our findings suggest that high allostatic load is associated with a higher risk of cancer mortality among AA women with lower educational attainment, while no such association was observed among AA women with higher educational attainment. Thus, educational attainment plays a modifying role in the relationship between allostatic load and the risk of cancer death for AA women. Higher education can bring several benefits, including improved access to medical care and enhanced medical literacy, which in turn may help mitigate the adverse impact of AL and the heightened risk of cancer mortality among AA women.
Training needs assessment of hospital CEOs in a developing country: the example of Iran
Authors: Hosseini Seyede-Elahe , Jafari Mehdi , Nemati Ali , Rahmani Keyvan , Mahmoudian Payam , Ferdosi Masoud
Published: August 2023

Background

It is essential to identify the necessary competencies of hospital CEOs in order to improve the quality and efficiency of services they provide. Expert leadership skills and competencies can have a significant impact on the success of an organization, benefiting both patients and staff. This study aimed to assess the competencies and training needs of hospital CEOs in Iran public hospitals.

Methods

We conducted this cross-sectional analytical study through a self-assessment questionnaire, which was a web-based platform developed by the WHO country office in Iran, between July 2018 and September 2018. The questionnaire was completed by 180 hospital CEOs and included a core set of 81 items based on Assessing the Competency of Hospital CEO. These items were categorized into five superordinate categories: leadership, personality and quality of individual behavior, knowledge and business skills, social responsibility, and healthcare environment. In addition, we conducted focus groups with 30 hospital CEOs, supervisor assessments with 10 hospital managers, and interviews with 10 supervisors.

Results

Of the 180 questionnaires distributed, 78% were returned, and most respondents were medical specialists. The need for leadership competencies such as individual behavior skills and change management received the highest priority. Most respondents required training in management skills, including financial management, governance, strategic thinking, quality improvement, and disaster management.

Conclusion

Providing needs-based education is crucial, especially in developing countries. In this study, leadership and strategic thinking were found to be the most needed competencies among hospital CEOs in Iran. These findings serve as reference points for developing countries with similar backgrounds and healthcare environments as Iran.
Effects of simulation with problem-based learning (S-PBL) on nursing students’ clinical reasoning ability: based on Tanner’s clinical judgment model
Authors: Son Hae Kyoung
Published: August 2023

Background

Clinical reasoning ability, a complex cognitive and metacognitive process, is a crucial core competency required in nursing practice. Therefore, undergraduate nursing students should be provided with nursing education to strengthen their clinical reasoning ability based on real-life nursing scenarios.

Methods

This study was conducted using a quasi-experimental single-group pretest–posttest design. Three sessions (lasting three hours each) of Simulation with Problem-Based Learning (S-PBL) using high-risk obstetrics-gynecology scenarios were provided to 71 third-year nursing students of a university. The sessions were conducted from September to December 2022, and they aimed to strengthen their clinical reasoning ability. For data collection, an online survey was conducted using Rubric for Clinical Reasoning and learning satisfaction evaluation tool. Data were analyzed using descriptive statistics and repeated measures analysis of variance in SPSS.

Results

The mean score of clinical reasoning ability significantly increased from 29.42 (standard deviation: 4.62) out of 40 points in the pre-test to 32.28 (4.36), 33.44 (5.35), and 33.80 (5.91) after the first, second, and third S-PBL sessions, respectively (F = 61.668, p < .001). The learning satisfaction score was as high as 107.04 (12.66) out of 120 points.

Conclusion

This S-PBL program is an effective nursing education strategy to strengthen nursing students’ clinical reasoning ability. Future studies must examine learner variables and standardize the S-PBL design and operation process by comparison to a traditional teaching approach and a higher range of clincal reasoning ability.
Structured interviews on self-regulated learning strategies of medical students in the final year of medical school
Authors: Corazza Laura , Shirkhani Sepide , Berberat Pascal O , Wijnen-Meijer Marjo
Published: August 2023

Background

In the final year of medical school, the educational focus is on experiences in the clinical environment. This is where students acquire most of their practical knowledge for their future career and need to optimise their Self-Regulated Learning (SRL) strategies. Hence, the current study aims to explore which SRL strategies medical students use during their clerkships in different learning settings.

Methods

Structured interviews were conducted between May 2019 and December 2020 with 43 medical students during their final year in Munich, Germany. The students were surveyed about their SRL strategies. The transcribed data were thematically analysed using the measurements Strategy Use (SU) and Strategy Frequency (SF).

Results

Interview data were organized into 11 SRL strategy categories. The most used SRL strategy in general was “seeking information in the internet in form of a text” (SU: 1; SF: 2.605), with an e-learning tool; followed by “seeking social assistance from doctors” (SU: 0.977; SF: 1.884), and “seeking information in books” (SU: 0.884; SF: 1.419). There were differences in the usage of SRL in different learning contexts between female and male students. For example, 95.3% of students are “seeking social assistance from doctors” when having difficulties on the ward, but only 55.8% when they need help with written tasks (e.g. medical letter). The results show a difference in SRL usage when preparing for oral-practical (79.1% books) and written (97.7% e-learning tool) exam. However, it also appears that some students do not have SRL strategies for certain situations, mostly due to a lack of time.

Conclusion

Medical students in the clinical phase are adapting their SRL strategy to the learning situation. To better support students´ SRL, it is necessary to ensure availability for their preferred resources: e-learning tool and experienced physicians as supervisors. Future research should focus on strategies to handle the limited time during clerkships.
Rare diseases: why is a rapid referral to an expert center so important?
Authors: Willmen Tina , Willmen Lukas , Pankow Anne , Ronicke Simon , Gabriel Heinz , Wagner Annette Doris
Published: August 2023

Background

Patients with rare diseases usually go through years of diagnostic odysseys. The large number of rare diseases and the associated lack of expertise pose a major challenge to physicians. There are few physicians dealing with patients with rare diseases and they usually work in a limited number of specialized centers. The aim of this study was to evaluate the diagnostic efficiency of an expert center.

Methods

The diagnostic pathway of 78 patients of the outpatient clinic for rare inflammatory systemic diseases with renal involvement was analyzed retrospectively. For this purpose, each examination day was documented with the corresponding examinations performed from the onset of initial symptoms. Three time points were considered: The time when patients first visited a physician with symptoms, the time when patients consulted an expert, and the time when they received the correct diagnosis. In addition, it was documented whether the diagnosis could be made without the expert, or only with the help of the expert. The examinations that confirmed the diagnosis were also documented for each patient.

Results

A correct diagnosis was made without the help of the expert in only 21% of cases. Each patient visited an average of 6 physicians before consulting the expert. Targeted diagnostics enabled the expert to make the correct diagnosis with an average of seven visits, or one inpatient stay. However, referral to the expert took an average of 4 years.

Conclusion

The data show that rapid and targeted diagnostics were possible in the expert center due to the available expertise and the interdisciplinary exchange. Early diagnosis is of great importance for many patients, as an early and correct therapy can be decisive for the course of the disease.
Cape York Kidney Care: service description and baseline characteristics of a client-centred multidisciplinary specialist kidney health service in remote Australia
Authors: Miller Andrea , Brown Leanne , Tamu Clara , Cairns Alice
Published: August 2023

Background

Chronic Kidney disease (CKD) is over-represented amongst First Nation people with more than triple the rate of CKD in those aged 15 years and over. The impact of colonisation, including harmful experiences of health practices and research, has contributed to these health inequities. Cape York Kidney Care (CYKC) has been created as an unique service which provides specialist care that aims to centre the client within a multidisciplinary team that is integrated within the primary care setting of the remote health clinics in six communities in western Cape York, Australia. This research aims to describe the Cape York Kidney Care service delivery model, and baseline service data, including aggregated client health measures.

Methods

The model of care is described in detail. Review of the first 12 months of service provision has been undertaken with client demographic and clinical profile baseline data collected including kidney health measures. Participants are adults (> 18 years if age) with CKD grades 1–5. This data has been de-identified and aggregated.

Results

CYKC reviewed 204 individuals, with 182 not previously been reviewed by specialist kidney health services. Three quarters of clients identified as Aboriginal. The average age was 55 with a high level of comorbidity, with majority having a history of hypertension and Type 2 diabetes (average Hba1c 8.2%). Just under one third had cardiovascular disease. A large proportion of people had either Grade 2 CKD (32%) or Grade 3 CKD (~ 30%), and over half had severely increased albuminuria (A3), with Type 2 diabetes being the predominant presumed cause of CKD. Most clients did not meet evidence-based targets for diabetes, blood pressure or lipids and half were self-reported smokers. The proportion of clients reviewed represents 6.2% of the adult population in the participating First Nation communities.

Conclusion

The CYKC model was able to target those clients at high risk of progression and increase the number of people with chronic kidney disease reviewed by specialist kidney services within community. Baseline data demonstrated a high burden of chronic disease that subsequently will increase risk of CKD progression and cardiovascular disease. People were seen to have more severe disease at younger ages, with a substantial number demonstrating risk factors for rapid progression of kidney disease including poorly controlled Type 2 diabetes and severely increased albuminuria. Further evaluation concerning implementation challenges, consumer and community satisfaction, and health outcomes is required.
Assessing patient partnership among emergency departments in France: a cross-sectional study
Authors: Sagnol Geoffrey , Haesebaert Julie , Termoz Anne , Michel Philipe , Schott Anne-Marie , Potinet Véronique , Pomey Marie-Pascale , Tazarourte Karim , Douplat Marion
Published: August 2023

Objectives

This study aims to describe the use of patient partnership, as defined by the Montreal Model, in emergency departments (EDs) in France and report the perception of patient partnership from both the practitioner and patient perspectives.

Methods

This cross-sectional study was conducted between July 2020 and October 2020. First, a survey was sent to 146 heads of EDs in both teaching hospitals and non-teaching hospitals in France to assess the current practices in terms of patient partnership in service organization, research, and teaching. The perceived barriers and facilitators of the implementation of such an approach were also recorded. Then, semi-structured telephone interviews were carried out with patients involved in a service re-organization project.

Results

A total of 48 answers (response rate 32.9%) to the survey were received; 33.3% of respondents involved patients in projects relating to service re-organization, 20.8% involved patients in teaching projects, and 4.2% in research projects. Overall, 60.4% of the respondents were willing to involve patients in re-organization or teaching projects. The main barriers mentioned for establishing patient partnership were difficulties regarding patient recruitment and lack of time. The main advantages mentioned were the improvement in patient/caregiver relationship and new ideas to improve healthcare. When interviewed, patients mentioned the desire to improve healthcare and the necessity to involve people with different profiles and backgrounds. A too important personal commitment was the most frequently raised barrier to their engagement. All the patients recognized their positive role, and more generally, the positive role of patient engagement in service re-organization.

Conclusion

Although this preliminary study indicates a rather positive perception of patient partnership among heads of EDs in France and partner patients, this approach is still not widely applied in practice.
Identification of basement membrane-related biomarkers associated with the diagnosis of osteoarthritis based on machine learning
Authors: Huang Xiaojing , Meng Hongming , Shou Zeyu , Yu Jiahuan , Hu Kai , Chen Liangyan , Zhou Han , Bai Zhibiao , Chen Chun
Published: August 2023

Background

Osteoarthritis is a very common clinical disease in middle-aged and elderly individuals, and with the advent of ageing, the incidence of this disease is gradually increasing. There are few studies on the role of basement membrane (BM)-related genes in OA.

Method

We used bioinformatics and machine learning methods to identify important genes related to BMs in OA patients and performed immune infiltration analysis, lncRNA‒miRNA-mRNA network prediction, ROC analysis, and qRT‒PCR.

Result

Based on the results of machine learning, we determined that LAMA2 and NID2 were the key diagnostic genes of OA, which were confirmed by ROC and qRT‒PCR analyses. Immune analysis showed that LAMA2 and NID2 were closely related to resting memory CD4 T cells, mast cells and plasma cells. Two lncRNAs, XIST and TTTY15, were simultaneously identified, and lncRNA‒miRNA‒mRNA network prediction was performed.

Conclusion

LAMA2 and NID2 are important potential targets for the diagnosis and treatment of OA.
Acute cigarette smoke exposure leads to higher viral infection in human bronchial epithelial cultures by altering interferon, glycolysis and GDF15-related pathways
Authors: Wang Ying , Ninaber Dennis K. , Faiz Alen , van der Linden Abraham C. , van Schadewijk Annemarie , Lutter René , Hiemstra Pieter S. , van der Does Anne M. , Ravi Abilash
Published: August 2023

Background

Acute exacerbations of chronic inflammatory lung diseases, such as chronic obstructive pulmonary disease (COPD), are frequently associated with rhinovirus (RV) infections. Despite these associations, the pathogenesis of virus-induced exacerbations is incompletely understood. We aimed to investigate effects of cigarette smoke (CS), a primary risk factor for COPD, on RV infection in airway epithelium and identify novel mechanisms related to these effects.

Methods

Primary bronchial epithelial cells (PBEC) from COPD patients and controls were differentiated by culture at the air–liquid interface (ALI) and exposed to CS and RV-A16. Bulk RNA sequencing was performed using samples collected at 6 and 24 h post infection (hpi), and viral load, mediator and l-lactate levels were measured at 6, 24 and 48hpi. To further delineate the effect of CS on RV-A16 infection, we performed growth differentiation factor 15 (GDF15) knockdown, l-lactate and interferon pre-treatment in ALI-PBEC. We performed deconvolution analysis to predict changes in the cell composition of ALI-PBEC after the various exposures. Finally, we compared transcriptional responses of ALI-PBEC to those in nasal epithelium after human RV-A16 challenge.

Results

CS exposure impaired antiviral responses at 6hpi and increased viral replication at 24 and 48hpi in ALI-PBEC. At 24hpi, CS exposure enhanced expression of RV-A16-induced epithelial interferons, inflammation-related genes and CXCL8. CS exposure increased expression of oxidative stress-related genes, of GDF15, and decreased mitochondrial membrane potential. GDF15 knockdown experiments suggested involvement of this pathway in the CS-induced increase in viral replication. Expression of glycolysis-related genes and l-lactate production were increased by CS exposure, and was demonstrated to contribute to higher viral replication. No major differences were demonstrated between COPD and non-COPD-derived cultures. However, cellular deconvolution analysis predicted higher secretory cells in COPD-derived cultures at baseline.

Conclusion

Altogether, our findings demonstrate that CS exposure leads to higher viral infection in human bronchial epithelium by altering not only interferon responses, but likely also through a switch to glycolysis, and via GDF15-related pathways.
Dissemination of the high-risk cloneST147 carbapenem-resistant klebsiella pneumoniae from a local tertiary care hospital in the Republic of Korea
Authors: Park Jungsun , Shin Eunkyung , Hwang Gwang Rip , Kim Min-Kyeong , Joo Seongjae , Jeong Hyun Ju , Kim Jin Seok , Yoo Jaeil , Kim Junyoung
Published: August 2023

Background

The emergence of carbapenem-resistant Enterobacterales (CRE) infections is rapidly increasing and represents a serious public threat. In 2020, a total of 16,883 carbapenemase-producing Enterobacterales strains were collected; among these isolates, 21 strains were repeatedly isolated in a local tertiary care hospital.

Methods

Antimicrobial susceptibility testing was performed using the broth microdilution method. All 21 strains of CRKP were analyzed by PFGE after XbaI digestion. The 21 CRKP strains were sequenced on the Illumina Miseq and Oxford Nanopore GridION platforms.

Results

These 21 CRKP isolates showed an identical antimicrobial resistance profile, including resistance to ampicillin, carbapenems, cephems, chloramphenicol, fluoroquinolone, macrolides and trimethoprim/sulfamethoxazole. Based on whole-genome analysis, these 21 CRKP isolates shared a common genetic structure (ISAba125-IS630-blaNDM−1-bleMBL) and harbored additional resistance determinants (blaOXA−1, blaCTX−M−15, blaSHV−11, blaSHV−67, aac(6’)-Ib-cr, qnrS1, OqxA, OqxB, catB3, mph(A), sul1, and dfrA12) and mutations in the quinolone resistance-determining regions of gyrA (S83I) and parC (S80I). These isolates belonged to the ST147 and KL64 capsular types, which were carried on IncFIB replicon plasmids. The 21 CRKP strains collected from one hospital were divided into five PFGE patterns, and they were closely related with a minimum similarity value of 95.2%. These isolates were found to be highly related based on the presence of between 2 and 27 SNPs.

Conclusions

These findings indicate that NDM-1-producing K. pneumoniae ST147 may have been introduced via a common source, implying nosocomial transmission; furthermore, continuous monitoring is necessary to prevent endemic transmission.
Cell unit-inspired natural nano-based biomaterials as versatile building blocks for bone/cartilage regeneration
Authors: Wang Fuxiao , Gu Zhengrong , Yin Zhifeng , Zhang Wencai , Bai Long , Su Jiacan
Published: August 2023

The regeneration of weight-bearing bone defects and critical-sized cartilage defects remains a significant challenge. A wide range of nano-biomaterials are available for the treatment of bone/cartilage defects. However, their poor compatibility and biodegradability pose challenges to the practical applications of these nano-based biomaterials. Natural biomaterials inspired by the cell units (e.g., nucleic acids and proteins), have gained increasing attention in recent decades due to their versatile functionality, compatibility, biodegradability, and great potential for modification, combination, and hybridization. In the field of bone/cartilage regeneration, natural nano-based biomaterials have presented an unparalleled role in providing optimal cues and microenvironments for cell growth and differentiation. In this review, we systematically summarize the versatile building blocks inspired by the cell unit used as natural nano-based biomaterials in bone/cartilage regeneration, including nucleic acids, proteins, carbohydrates, lipids, and membranes. In addition, the opportunities and challenges of natural nano-based biomaterials for the future use of bone/cartilage regeneration are discussed.
Ceramide synthesis regulates biogenesis and packaging of exosomal MALAT1 from adipose derived stem cells, increases dermal fibroblast migration and mitochondrial function
Authors: Kong Xaioyuan , Patel Niketa A. , Chalfant Charles E. , Cooper Denise R.
Published: August 2023

Background

The function of exosomes, small extracellular vesicles (sEV) secreted from human adipose-derived stem cells (ADSC), is becoming increasingly recognized as a means of transferring the regenerative power of stem cells to injured cells in wound healing. Exosomes are rich in ceramides and long noncoding RNA (lncRNA) like metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). We identified putative ceramide responsive cis-elements (CRCE) in MALAT1. We hypothesized that CRCE respond to cellular ceramide levels to regulate sEV MALAT1 packaging. MALAT1 levels by many cells exceed those of protein coding genes and it’s expression is equally high in exosomes. Ceramide also regulates exosome synthesis, however, the contents of exosome cargo via sphingomyelinase and ceramide synthase pathways has not been demonstrated.

Methods

ADSC were treated with an inhibitor of sphingomyelinase, GW4869, and stimulators of ceramide synthesis, C2- and C6-short chain ceramides, prior to collection of conditioned media (CM). sEV were isolated from CM, and then used to treat human dermal fibroblast (HDF) cultures in cell migration scratch assays, and mitochondrial stress tests to evaluate oxygen consumption rates (OCR).

Results

Inhibition of sphingomyelinase by treatment of ADSC with GW4869 lowered levels of MALAT1 in small EVs. Stimulation of ceramide synthesis using C2- and C6- ceramides increased cellular, EVs levels of MALAT1. The functional role of sEV MALAT1 was evaluated in HDF by applying EVs to HDF. Control sEV increased migration of HDF, and significantly increased ATP production, basal and maximal respiration OCR. sEV from GW4869-treated ADSC inhibited cell migration and maximal respiration. However, sEV from C2- and C6-treated cells, respectively, increased both functions but not significantly above control EV except for maximal respiration. sEV were exosomes except when ADSC were treated with GW4869 and C6-ceramide, then they were larger and considered microvesicles.

Conclusions

Ceramide synthesis regulates MALAT1 EV content. Sphingomyelinase inhibition blocked MALAT1 from being secreted from ADSC EVs. Our report is consistent with those of MALAT1 increasing cell migration and mitochondrial MALAT1 altering maximal respiration in cells. Since MALAT1 is important for exosome function, it stands that increased exosomal MALAT1 should be beneficial for wound healing as shown with these assays.
The emergence of influenza B as a major respiratory pathogen in the absence of COVID-19 during the 2021–2022 flu season in China
Authors: Chang De , Lin Mingui , Song Ning , Zhu Zhantao , Gao Jing , Li Shujun , Liu Hongmei , Liu DeZhi , Zhang Yu , Sun Wenkui , Zhou Xuan , Yang Bin , Li Yongjun , Wang Lili , Xiao Zhiqing , Li Kailong , Xing Lihua , Xie Lixin , Sharma Lokesh
Published: August 2023

Background

The emergence of COVID-19 and the implementation of preventive measures and behavioral changes have led to a significant decrease in the prevalence of other respiratory viruses. However, the manner in which seasonal viruses will reemerge in the absence of COVID-19-related restrictions remains unknown.

Methods

Patients presenting with influenza-like illness in two hospitals in Beijing were subjected to testing for COVID-19, influenza A, and influenza B to determine the causative agent for viral infections. The prevalence of influenza B across China was confirmed using data from the Centers for Disease Control, China (China CDC). Clinical characteristics, laboratory findings, imaging results, and mortality data were collected for a cohort of 70 hospitalized patients with confirmed influenza B from 9 hospitals across China.

Results

Starting from October 2021, a substantial increase in the number of patients visiting the designated fever clinics in Beijing was observed, with this trend continuing until January 2022. COVID-19 tests conducted on these patients yielded negative results, while the positivity rate for influenza rose from approximately 8% in October 2021 to over 40% by late January 2022. The cases started to decline after this peak. Data from China CDC confirmed that influenza B is a major pathogen during the season. Sequencing of the viral strain revealed the presence of the Victoria-like lineage of the influenza B strain, with minor variations from the Florida/39/2018 strain. Analysis of the hospitalized patients' characteristics indicated that severe cases were relatively more prevalent among younger individuals, with an average age of 40.9 ± 24.1 years. Among the seven patients who succumbed to influenza, the average age was 30 ± 30.1 years. These patients exhibited secondary infections involving either bacterial or fungal pathogens and displayed elevated levels of cell death markers (such as LDH) and coagulation pathway markers (D-dimer).

Conclusion

Influenza B represents a significant infection threat and can lead to substantial morbidity and mortality, particularly among young patients. To mitigate morbidity and mortality rates, it is imperative to implement appropriate vaccination and other preventive strategies.
MKRN1 promotes colorectal cancer metastasis by activating the TGF-β signalling pathway through SNIP1 protein degradation
Authors: Zhang Yi , Li Qin-shan , Liu Hong-lin , Tang Hong-ting , Yang Han-lin , Wu Dao-qiu , Huang Yu-ying , Li Li-cheng , Liu Li-hong , Li Meng-xing
Published: August 2023

Background

The Makorin ring finger protein 1 (MKRN1) gene, also called RNF61, is located on the long arm of chromosome 7 and is a member of the RING finger protein family. The E3 ubiquitin ligase MKRN1 is closely linked to tumour development, but the exact mechanism needs to be elucidated. In this study, we aimed to investigate the specific mechanism and role of MKRN1 in colorectal cancer (CRC) development.

Methods

MKRN1 expression in CRC was analysed using the Cancer Cell Line Encyclopaedia and the Cancer Genome Atlas (TCGA) databases. Rectal tumour tissues were frozen to explore the MKRN1 expression in CRC and its clinical significance. The impact of MKRN1 on CRC cell proliferation and migration was observed using CCK8, colony formation, wound healing, and transwell assays. A combination of MKRN1 quantitative proteomics, ubiquitination modification omics analysis, and a string of in vitro and in vivo experiments revealed the potential mechanisms by which MKRN1 regulates CRC metastasis.

Results

MKRN1 expression was significantly elevated in CRC tissues compared to paracancerous tissues and was positively linked with prognosis (P < 0.01). MKRN1 downregulation inhibits CRC cell proliferation, migration, and invasion. Conversely, MKRN1 overexpression promotes the proliferation, migration, and invasion of CRC cells. Mechanistically, MKRN1 induces epithelial-mesenchymal transition (EMT) in CRC cells via ubiquitination and degradation of Smad nuclear-interacting protein 1 (SNIP1). Furthermore, SNIP1 inhibits transforming growth factor-β (TGF-β) signalling, and MKRN1 promotes TGF-β signalling by degrading SNIP1 to induce EMT in CRC cells. Finally, using conditional knockout mice, intestinal lesions and metastatic liver microlesions were greatly reduced in the intestinal knockout MKRN1 group compared to that in the control group.

Conclusions

High MKRN1 levels promote TGF-β signalling through ubiquitination and degradation of SNIP1, thereby facilitating CRC metastasis, and supporting MKRN1 as a CRC pro-cancer factor. The MKRN1/SNIP1/TGF-β axis may be a potential therapeutic target in CRC.
Roles of follicle stimulating hormone and sphingosine 1-phosphate co-administered in the process in mouse ovarian vitrification and transplantation
Authors: Wang Fei , Tian Yuan , Huang Liwen , Qin Tian , Ma Wenye , Pei Chengbin , Xu Bo , Han Hang , Liu Xinrui , Pan Pengge , Yu Xiaoli , Chang Qin , Wang Yanrong , Zhang Shuya , Pei Xiuying
Published: August 2023

Some major challenges of ovarian tissue vitrification and transplantation include follicle apoptosis induced by cryopreservation and ischemia-reperfusion injury, as well as ovarian follicle loss during post-transplantation. This research aimed to investigate the protective effects and underlying mechanisms of follicle-stimulating hormone (FSH) and Sphingosine-1-phosphate (S1P) on vitrified and post-transplantation ovaries. Ovaries from 21-day-old mice were cryopreservation by vitrification with 0.3 IU/mL FSH, 2 µM S1P, and 0.3 IU/mL FSH + 2 µM S1P, respectively, for follicle counting and detection of apoptosis-related indicators. The results demonstrated that FSH and S1P co-intervention during the vitrification process could preserve the primordial follicle pool and inhibit follicular atresia by suppressing cell apoptosis. The thawed ovaries were transplanted under the renal capsule of 6–8 week-old ovariectomized mice and removed 24 h or 7 days after transplantation. The results indicated that FSH and S1P co-intervention can inhibit apoptosis and autophagy in ovaries at 24 h after transplantation, and promote follicle survival by up-regulating Cx37 and Cx43 expression, enhanced angiogenesis in transplanted ovaries by promoting VEGF expression, as well as increased the E2 levels to restore ovarian endocrine function at 7 days after transplantation. The hypoxia and ischemia cell model was established by CoCl2 treatment for hypoxia in human granulosa-like tumor cell line (KGN), as well as serum-free culture system was used for ischemia. The results confirmed that ischemia-hypoxia-induced apoptosis in ovarian granulosa cells was reduced by FSH and S1P co-intervention, and granulosa cell autophagy was inhibited by up-regulating the AKT/mTOR signaling pathway. In summary, co-administration of FSH and S1P can maintain ovarian survival during ovarian vitrification and increase follicle survival and angiogenesis after transplantation.
Protocol of a multicenter, single-blind, randomized, parallel controlled trial evaluating the effect of microbiological rapid on-site evaluation (M-ROSE) guiding anti-infection treatment in patients with severe hospital-acquired pneumonia
Authors: Wang Xiuli , Wang Kaifei , Xie Fei , Han Zhihai , Liu Yuhong , Pan Lei , Zhu Guangfa , Cao Zhixin , Yan Peng , Xiao Li , Duan Zhimei , Hu Ye , Xiao Kun , Chen Xuxin , Fu Han , Shi Yinghan , Song Yuwei , Han Xiaobo , Xie Wuxiang , Xie Lixin
Published: August 2023

Introduction

The mortality rate of hospitalized patients with severe hospital-acquired pneumonia (SHAP) remains high. Empirical broad-spectrum antibiotic coverage and the misuse of high-grade antibiotics could lead to the emergence of multi-drug and even pandrug-resistant bacteria. In addition to metagenomic next-generation sequencing (mNGS), microbiological rapid on-site evaluation (M-ROSE) might be a useful technique to identify the pathogens in the early stage; however, the effect of M-ROSE guiding anti-infection treatment on prognostic outcomes of SHAP patients is still unclear.

Methods/design

This is a multicenter, single-blind, prospective, randomized controlled trial to evaluate the effect of M-ROSE guiding anti-infection treatment in SHAP patients, which will provide new strategies for the prevention and control of clinical multi-drug resistance bacteria. A total of 166 patients with SHAP, aged 18 years and over, will be recruited from seven centers in Beijing and randomly assigned to the intervention group (M-ROSE combined with mNGS) or the control group (mNGS only) in a 1:1 ratio using the central randomization system. Patients in the intervention group will accept M-ROSE and mNGS analysis, and the control group will accept mNGS analysis. Individualized anti-infective treatment and routine treatment will be selected according to the analysis results. The primary outcome is the ICU outcome (mortality). The safety of the intervention measures will be evaluated during the entire trial period. This trial will be the first randomized controlled trial to evaluate the effect of M-ROSE guiding treatment on mortality in patients with SHAP and may change the prevalence of multi-drug resistant bacteria.

Ethics and dissemination

This trial adheres to the Declaration of Helsinki and guidelines of Good Clinical Practice. Signed informed consent will be obtained from all participants. The trial has been approved by the Chinese PLA General Hospital (Approval Number: 20220322001).

Trial registration

ClinicalTrials.gov NCT05300776. Registered on 25 March 2022.
Study protocol: effects of treatment expectation toward repetitive transcranial magnetic stimulation (rTMS) in major depressive disorder—a randomized controlled clinical trial
Authors: Steiner Katharina M. , Timmann Dagmar , Bingel Ulrike , Kunkel Angelika , Spisak Tamas , Schedlowski Manfred , Benson Sven , Engler Harald , Scherbaum Norbert , Koelkebeck Katja
Published: August 2023

Background

Patients’ expectations toward any given treatment are highly important for the effectiveness of such treatment, as has been demonstrated for several disorders. In particular, in major depressive disorder (MDD), one of the most frequent and most serious mental disorders with severe consequences for the affected, the augmentation of available treatment options could mean a ground-breaking success. Repetitive transcranial magnetic stimulation (rTMS), a new, non-invasive, and well-tolerated intervention with proven effects in the treatment of MDD, appears particularly suitable in this context as it is assumed to exert its effect via structures implicated in networks relevant for both expectation and depression.

Methods

All patients will receive rTMS according to its approval. Half of the patients will be randomized to a psychological intervention, which is a comprehensive medical consultation aiming to improve positive treatment expectations; the control group will receive a conventional informed consent discussion (in the sense of a treatment-as-usual condition). As outcome parameters, instruments for both self-assessment and external assessment of depression symptoms will be applied. Furthermore, psycho-immunological parameters such as inflammation markers and the cortisol awakening response in saliva will be investigated. Resting-state functional magnetic resonance imaging (rs fMRI) will be performed to analyze functional connectivity, including the cerebellum, and to identify neuronal predictors of expectation effects. In addition, possible cerebellar involvement will be assessed based on a cerebellar-dependent motor learning paradigm (i.e., eyeblink conditioning).

Discussion

In this study, the effects of treatment expectations towards rTMS are investigated in patients with MDD. The aim of this study is to identify the mechanisms underlying the expectation effects and, beyond that, to expand the potential of non-invasive and well-tolerated treatments of MDD.

Trial registration

German Registry of Clinical Studies (DRKS DRKS00028017. Registered on 2022/03/07. URL: https://www.drks.de/drks_web/.