bluuebunny/crossref_metadata_2025 huggingface dataset:
Multidrug-resistant Aeromonas bacteria prevalence in Nile tilapia broodstock
Authors: Sherif Ahmed H. , Kassab Amina S.
Published: March 2023

Background

Aeromonas hydrophila is an opportunistic pathogen. Thus, it has received significant attention mainly in the fish sectors with high production scales. Nile tilapia broodstock confined in the environment of fish hatcheries can be stressed. Hence, they are vulnerable to A. hydrophila.

Results

Sequencing of the gyr B gene revealed the presence of 18 different A. hydrophila strains (kdy 10,620–10,637), which were deposited in the NCBI under accession numbers ON745861–ON745878. The median lethal doses of the isolates ranged from 2.62 × 104 to 3.02 × 106 CFU/mL. Antibiotic resistant genes, sulfonamide (sul1) and tetracycline (tetA) were found in the eighteen isolates. Approximately 83.3% of A. hydrophila strains were sensitive to ciprofloxacin and florfenicol. Further, eight A. hydrophila strains had high MDR indices at 0.27–0.45. All isolates presented with hemolysin activity. However, only 72.22% of them had proteolytic activity, and only 61.11% could form biofilms. Bacterial isolates harbored different pattern virulence genes, the heat-stable cytotonic enterotoxin (ast), cytotoxic enterotoxin (act), and hemolysin (hly) genes were the most prevalent. Also, a trial to inhibit bacterial growth was conducted using titanium dioxide nanoparticles (TiO2 NPs) with three sizes (13, 32, and 123 nm). If A. hydrophila strains with a high MDR index were tested against TiO2 NPs (20 µg/mL) for 1, 12, and 24 h, those with a small size had a greater bactericidal action than large ones. Bacterial strains were inhibited at different percentages in response to TiO2 NP treatment.

Conclusions

Nile tilapia broodstock, mortality is associated with different A. hydrophila strains, which harbored virulent and MDR genes. Furthermore, TiO2 NPs had bactericidal activity, thereby resulting in a considerable reduction in bacterial load.
Eubiotic effect of rifaximin is associated with decreasing abdominal pain in symptomatic uncomplicated diverticular disease: results from an observational cohort study
Authors: Ivashkin Vladimir , Shifrin Oleg , Maslennikov Roman , Poluektova Elena , Korolev Alexander , Kudryavtseva Anna , Krasnov George , Benuni Nona , Barbara Giovanni
Published: March 2023

Background

Rifaximin effectively treats symptomatic uncomplicated diverticular disease (SUDD) and has shown eubiotic potential (i.e., an increase in resident microbial elements with potential beneficial effects) in other diseases. This study investigated changes in the fecal microbiome of patients with SUDD after repeated monthly treatment with rifaximin and the association of these changes with the severity of abdominal pain.

Methods

This was a single-center, prospective, observational, uncontrolled cohort study. Patients received rifaximin 400 mg twice a day for 7 days per month for 6 months. Abdominal pain (assessed on a 4-point scale from 0 [no pain] to 3 [severe pain]) and fecal microbiome (assessed using 16 S rRNA gene sequencing) were assessed at inclusion (baseline) and 3 and 6 months. The Spearman’s rank test analyzed the relationship between changes in the gut microbiome and the severity of abdominal pain. A p-value ≤ 0.05 was considered statistically significant.

Results

Of the 23 patients enrolled, 12 patients completed the study and were included in the analysis. Baseline abdominal pain levels decreased significantly after 3 (p = 0.036) and 6 (p = 0.008) months of treatment with rifaximin. The abundance of Akkermansia in the fecal microbiome was significantly higher at 3 (p = 0.017) and 6 (p = 0.015) months versus baseline. The abundance of Ruminococcaceae (p = 0.034), Veillonellaceae (p = 0.028), and Dialister (p = 0.036) were significantly increased at 6 months versus baseline, whereas Anaerostipes (p = 0.049) was significantly decreased. The severity of abdominal pain was negatively correlated with the abundance of Akkermansia (r=-0.482; p = 0.003) and Ruminococcaceae (r=-0.371; p = 0.026) but not with Veillonellaceae, Dialister, or Anaerostipes. After 3 months of rifaximin, abdominal pain was significantly less in patients with Akkermansia in their fecal microbiome than in patients without Akkermansia (p = 0.022).

Conclusion

The eubiotic effect of rifaximin was associated with decreased abdominal pain in patients with SUDD.
Clinical-radiomics models based on plain X-rays for prediction of lung metastasis in patients with osteosarcoma
Authors: Yin Ping , Zhong Junwen , Liu Ying , Liu Tao , Sun Chao , Liu Xiaoming , Cui Jingjing , Chen Lei , Hong Nan
Published: March 2023

Objectives

Osteosarcoma (OS) is the most common primary malignant bone tumor in adolescents. Lung metastasis (LM) occurs in more than half of patients at different stages of the disease course, which is one of the important factors affecting the long-term survival of OS. To develop and validate machine learning radiomics model based on radiographic and clinical features that could predict LM in OS within 3 years.

Methods

486 patients (LM = 200, non-LM = 286) with histologically proven OS were retrospectively analyzed and divided into a training set (n = 389) and a validation set (n = 97). Radiographic features and risk factors (sex, age, tumor location, etc.) associated with LM of patients were evaluated. We built eight clinical-radiomics models (k-nearest neighbor [KNN], logistic regression [LR], support vector machine [SVM], random forest [RF], Decision Tree [DT], Gradient Boosting Decision Tree [GBDT], AdaBoost, and extreme gradient boosting [XGBoost]) and compared their performance. The area under the receiver operating characteristic curve (AUC) and accuracy (ACC) were used to evaluate different models.

Results

The radscore, ALP, and tumor size had significant differences between the LM and non-LM groups (tradscore = -5.829, χ2ALP = 97.137, tsize = -3.437, P < 0.01). Multivariable LR analyses showed that ALP was an important indicator for predicting LM of OS (odds ratio [OR] = 7.272, P < 0.001). Among the eight models, the SVM-based clinical-radiomics model had the best performance in the validation set (AUC = 0.807, ACC = 0.784).

Conclusion

The clinical-radiomics model had good performance in predicting LM in OS, which would be helpful in clinical decision-making.
Gastric ulcer and duodenitis associated with coinfection of human herpesvirus-8 and cytomegalovirus in a renal transplant recipient: a case report
Authors: Lee Sik , Kim Kyoung Min , Hwang Hong Pil , Hwang Jeong-Hwan
Published: March 2023

Background

The coinfection between cytomegalovirus (CMV) and either human herpesvirus‐6 (HHV‐6) or HHV-7 in renal transplant recipients is well known; however, there have been few reports of coinfection of CMV associated with HHV-8. This paper presents a first case of acute gastric ulcer and duodenitis associated with CMV and HHV‐8 coinfection after renal transplantation.

Case presentation

A 33-year-old male with a history of kidney transplantation was admitted to hospital because of postural epigastric pain. The recipient was CMV seropositive prior to transplantation and received trimethoprim-sulfamethoxazole without universal prophylaxis. Approximately 5 months after renal transplant, the recipient complained postural epigastric pain. An endoscopy revealed diffuse ulcerative lesions in the lower body and in the antrum of the stomach, as well as several erythematous mucosal lesions in the duodenum. Histopathologic examination identified CMV inclusions consistent with invasive CMV disease and immunohistochemical staining showed positive results for HHV-8 and CMV. No tumorous diseases such as Kaposi’s sarcoma were detected. After 3 weeks of intravenous ganciclovir treatment, we observed that serum CMV PCR remained within the normal range and clinical symptoms improved. A follow-up endoscopy performed 3 weeks later showed that the severity of the above mentioned lesions had improved.

Conclusions

We report the first case of a renal transplant recipient diagnosed with acute gastric ulcer and duodenitis associated with coinfection of CMV and HHV-8. Ganciclovir appears to be effective in diseases associated with coinfection of CMV and HHV-8.
Stability of sensor-based gait parameters reassessed after a period of one year in people with multiple sclerosis
Authors: Müller Roy , Hamacher Daniel , Keune Philipp M. , Oschmann Patrick
Published: March 2023

Background

Currently, there are several studies showing that wearable inertial sensors are highly sensitive in the detection of gait disturbances in people with multiple sclerosis (PwMS), showing excellent reliability within one or 7–14 days. However, it is not known how stable these gait parameters remain over a longer period of time. This is surprising, because many treatments last longer than two weeks. Thus, the purpose of the current study was to examine gait parameters obtained by means of wearable inertial sensors during a 6-min walk and to reassess these parameters after a period of one year.

Methods

Fifty PwMS (without a relapse or a recent change in the Expanded Disability Status Scale (EDSS) or treatment) and 20 healthy participants were examined at two assessment points (interval between assessments: 14.4 ± 6.6 months). At each assessment point, all participants had to complete a 6-min walking test, an observer-rater test (Berg Balance Scale, BBS) and a Timed-up and Go Test (TUG). To measure mean gait parameters (i.e. walking speed, stride length, stride time, the duration of the stance and swing phase and minimum toe-to-floor distance), as well as the intraindividual standard deviation of each mean gait parameter, wearable inertial sensors were utilized.

Results

We found that even after one year all mean gait parameters showed excellent Intraclass Correlation Coefficients (ICC between 0.75 and 0.95) in PwMS. Looking at MS subgroups, the ICCs were slightly higher in MS subgroup 2 (EDSS 2.0–5.0) than those in MS subgroup 1 (EDSS 0.0–1.5) and healthy controls. Compared to the mean gait parameters, parameters of gait variability showed only good-to-fair ICC values in PwMS. Concerning BBS and TUG, the ICC values after one year were close to the ICC values of the measured mean gait parameters.

Conclusions

Due to the excellent stability of mean gait parameters after one year, these sensor-based gait parameters can be identified as clinically relevant markers to evaluate treatment effects over a longer (several months) period of time in MS.
Successful mechanical thrombectomy in acute bilateral M1 middle cerebral artery occlusion: a case report and literature review
Authors: Li Zhiqiang , Wu Shuhui , Zhao Shuzhi , Li Ning , Ma Weibin , Jiang Guisheng , Liu Lingling , Jing Guoxian
Published: March 2023

Background

Acute bilateral occlusion of the middle cerebral artery (MCA) is a very rare condition, and most cases are accompanied by a poor prognosis. However, mechanical thrombectomy (MT) for bilateral MCA is challenging. Here, we report a case of acute unilateral MCA occlusion with sequential acute occlusion of the bilateral MCA during intravenous thrombolysis (IVT). We urgently performed bilateral MT of the MCA and effective recanalization.

Case presentation

The patient is a 73-year-old man who complained of a sudden adverse influence on speech and an inability to move his left limb for 2 h. He had a history of paroxysmal atrial fibrillation, but had never used any anticoagulants before. Head and neck computed tomography angiography (CTA) showed embolism in the right M1 MCA. During intravenous alteplase thrombolytic therapy, the patient suddenly became unconscious. Cerebral angiography showed occlusion of the M1 segment of the bilateral MCA in the patients. MT of the bilateral MCA was performed using a combination of a stent retriever and an aspiration catheter with mTici 3 revascularization. On the second day, the patient became conscious, although he had remaining symptoms of speech insufficiency and weakness of the left limb. The mRS score was 2 90 days after the operation.

Conclusions

Acute bilateral occlusion of the M1 segment of the MCA is extremely rare and is accompanied by high morbidity and high mortality. Intravenous alteplase thrombolysis can increase the risk of atrial thrombus shedding in patients with atrial fibrillation, so patients with acute bilateral MCA occlusion in the M1 segment chose direct MT or bridging therapy, which remains controversial, and the sequence of MT remains to be discussed. Nevertheless, early endovascular treatment can decrease the morbidity and mortality of such patients.
Tolerability of concurrent external beam radiotherapy and [177Lu]Lu-PSMA-617 for node-positive prostate cancer in treatment naïve patients, phase I study (PROQURE-I trial)
Authors: van der Sar Esmée C. A. , Braat Arthur J. A. T. , van der Voort- van Zyp Jochem R. N. , van der Veen Betty S. , van Leeuwen Pim J. , de Vries-Huizing Daphne M. V. , Hendrikx Jeroen M. A. , Lam Marnix G. E. H. , Vogel Wouter V.
Published: March 2023

Background

Prostate cancer patients with locoregional lymph node disease at diagnosis (N1M0) still have a limited prognosis despite the improvements provided by aggressive curative intent multimodal locoregional external beam radiation therapy (EBRT) with systemic androgen deprivation therapy (ADT). Although some patients can be cured and the majority of patients have a long survival, the 5-year biochemical failure rate is currently 29–47%. [177Lu]Lu-PSMA-617 has shown impressive clinical and biochemical responses with low toxicity in salvage setting in metastatic castration-resistant prostate cancer. This study aims to explore the combination of standard EBRT and ADT complemented with a single administration of [177Lu]Lu-PSMA-617 in curative intent treatment for N1M0 prostate cancer. Hypothetically, this combined approach will enhance EBRT to better control macroscopic tumour localizations, and treat undetected microscopic disease locations inside and outside EBRT fields.

Methods

The PROQURE-I study is a multicenter prospective phase I study investigating standard of care treatment (7 weeks EBRT and 3 years ADT) complemented with one concurrent cycle (three, six, or nine GBq) of systemic [177Lu]Lu-PSMA-617 administered in week two of EBRT. A maximum of 18 patients with PSMA-positive N1M0 prostate cancer will be included. The tolerability of adding [177Lu]Lu-PSMA-617 will be evaluated using a Bayesian Optimal Interval (BOIN) dose-escalation design. The primary objective is to determine the maximum tolerated dose (MTD) of a single cycle [177Lu]Lu-PSMA-617 when given concurrent with EBRT + ADT, defined as the occurrence of Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 grade three or higher acute toxicity. Secondary objectives include: late toxicity at 6 months, dosimetric assessment, preliminary biochemical efficacy at 6 months, quality of life questionnaires, and pharmacokinetic modelling of [177Lu]Lu-PSMA-617.

Discussion

This is the first prospective study to combine EBRT and ADT with [177Lu]Lu-PSMA-617 in treatment naïve men with N1M0 prostate cancer, and thereby explores the novel application of [177Lu]Lu-PSMA-617 in curative intent treatment. It is considered likely that this study will confirm tolerability as the combined toxicity of these treatments is expected to be limited. Increased efficacy is considered likely since both individual treatments have proven high anti-tumour effect as mono-treatments.

Trial registration

ClinicalTrials, NCT05162573. Registered 7 October 2021.
Negative regulation of CD44st by miR-138-5p affects the invasive ability of breast cancer cells and patient prognosis after breast cancer surgery
Authors: Jian Fang Xin , Bao Peng Xiao , Li Wang Fu , Cui Yan Hai , Hong Hang Guan
Published: March 2023

Objective

To investigate how the negative regulation of CD44st by miR-138-5p affects the invasive ability of breast cancer cell lines and prognosis in postoperative breast cancer patients.

Methods

RT-PCR, qRT-PCR, and western blot assays were used to detect the expression of CD44s, CD44v6, and CD44st at both mRNA and protein levels. The expression of miR-138-5p in breast cancer cell lines was also evaluated. The binding ability of miR-138-5p to CD44st was determined via a dual-luciferase assay. The CD44 protein expression in breast cancer tissues was detected using immunohistochemistry. A Transwell assay was used to detect the invasive ability of tumor cells. The correlation between CD44st and miR-138-5p mRNA expression in breast cancer tissues was evaluated using qRT-PCR, and the relationship between clinicopathological features was statistically analyzed.

Results

CD44s and CD44v6 were highly expressed in MDAMB-231 cell line, while CD44st was highly expressed in MCF-7/Adr and Skbr-3 cells. None of the CD44 isoforms were expressed in MCF-7 cells. The miR-138-5p was highly expressed in MCF-7 cells, but not in MCF-7/Adr, Skbr-3, and MDAMB-231 cells. The dual-luciferase assay suggested that miR-138-5p could bind to wild-type CD44st 3'-UTR, miR-138-5p overexpression significantly inhibited the expression level of CD44 protein in MCF-7/Adr cells, and miR-138-5p + CD44st (3'-UTR)-treated MCF-7/Adr and Skbr-3 cells were significantly less invasive than those in the control group (P < 0.05). RT-PCR results for 80 postoperative breast cancer patients showed that the mRNA expression rate for CD44st was higher in cancer tissues than in paracancerous tissues, and the expression rate of miR-138-5p was higher in paracancerous tissues than in cancerous tissues (P < 0.01). In cancer tissues, CD44st was negatively correlated with miR-138-5p expression, with correlation coefficient r = -0.76 (Pearson’s correlation), coefficient of determination R2 = 0.573, F = 106.89, and P < 0.001. The median overall survival value for patients in the low miR-138-5p expression group was 40.39 months [95% confidence interval (CI): 35.59–45.18 months] and 56.30 months (95% CI: 54.38–58.21 months) for patients in the high-expression group, with a log rank (Mantel-Cox) of 13.120, one degree of freedom, and P < 0.001.

Conclusion

In breast cancer cell lines, miR-138-5p negatively regulated expression of CD44st and affected the invasive ability of tumor cells and patient prognosis after breast cancer surgery.
Efficacy and safety analysis of TACE + sunitinib vs. sunitinib in the treatment of unresectable advanced renal cell carcinoma: a retrospective study
Authors: Lu Haohao , Ye Qing , Zheng Chuansheng , Fan Li , Xia Xiangwen
Published: March 2023

Background

Since renal cell carcinoma(RCC) is insensitive to conventional chemoradiotherapy, molecularly targeted drugs are commonly used treatments for unresectable advanced RCC. The aim of this study was to explore the efficacy and safety of TACE + sunitinib vs. sunitinib in the treatment of unresectable advanced RCC.

Methods

This study included 98 patients with unresectable advanced RCC who were treated in Union Hospital from January 2015 to December 2018, and they met the criteria. They were divided into two groups: TACE + Sunitinib group (N = 47) and Sunitinib group (N = 51). We conducted a retrospective study to analyze the efficacy and safety of the two groups of patients.

Results

(1)TACE + Sunitinib group: 4 patients (8.5%) achieved CR, 27 patients (57.5%) achieved PR, 9 patients (19.1%) achieved SD, and 7 patients (14.9%) achieved PD. Sunitinib group, 0 patients (0%) achieved CR, 20 patients (39.2%) achieved PR, 14 patients (27.5%) achieved SD, and 17 patients (33.3%) achieved PD. (P = 0.017) (2)ORR: TACE + sunitinib group, 66.0%; sunitinib group, 39.2%. (P = 0.009) (3)DCR: TACE + sunitinib group, 85.1%; sunitinib group, 66.7%. (P = 0.038) (4) In the TACE + sunitinib group, mPFS was 15.6 months, mOS was 35.0 months; in the sunitinib group, the mPFS was 10.9 months, mOS was 25.7 months. (P < 0.001) (5) The incidence of abdominal pain, fever, and vomiting was higher in the TACE + sunitinib group than in the sunitinib group (abdominal pain: 55.3% vs. 13.7%; fever: 61.7% vs. 7.8%; vomiting: 40.4% vs. 19.6%; P < 0.05). The technical success rate of TACE in TACE + Sunitinib group is 100%.

Conclusions

The TACE + sunitinib group had higher ORR and DCR, longer OS and PFS than the sunitinib alone group. TACE combined with sunitinib can play a complementary role and is a safe and effective treatment for advanced RCC.
The evaluation of locoregional tumoral involvement in the cooccurrence of hashimoto thyroiditis with papillary thyroid cancer: a case controlled study
Authors: Nasiri Shirzad , Yazd Seyed Mostafa Meshkati , Gholami Mahsa , Shahriarirad Sepehr , Sharghi Sina , Shahriarirad Reza
Published: March 2023

Background

Papillary thyroid carcinoma PTC is the most prevalent of all thyroid carcinomas. On the other hand, Hashimoto’s thyroiditis (HT), as part of the spectrum of autoimmune thyroid diseases, is a major cause of thyroid hypofunction worldwide. Several studies have aimed to indicate a possible correlation between PTC and HT over the years. This study aims to investigate the correlation between HT disease and PTC tumor invasion rate.

Method

In the present cross-sectional study, PTC patients with HT were selected among patients referred to the surgical ward of Shariati hospital from 2016 to 2019 and compared in terms of tumor invasion and central LN dissection. Also, a similar group of PTC patients without HT undergoing total thyroidectomy was selected for comparison. The tumor invasion rate was assessed based on invasion indices obtained from postoperative permanent pathology specimens. These indices included tumor type and size, number of involved LNs, lymphovascular involvement, perineural involvement, thyroid capsule involvement, multifocal or unifocal tumor, extrathyroidal proliferation, marginal status, and necrosis. Data were obtained and compared in the two groups with SPSS version 22.0 software.

Results

Based on the postoperative pathology reports, 50 (56.2%) PTC patients with Hashimoto thyroiditis were compared against 39 PTC patients without Hashimoto thyroiditis. No significant difference was found between the two groups regarding tumor invasion factors such as multifocality, lymphovascular invasion, marginal invasion, extrathyroidal invasion, capsular invasion, and necrosis.

Conclusion

HT could not be mentioned as an aggravating factor of PTC invasion based on the invasion factors evaluated in pathology specimens.
The association of employment status and unwanted job loss with maternal oral health experiences: findings from the pregnancy risk assessment monitoring system
Authors: Testa Alexander , Gimeno Ruiz de Porras David
Published: March 2023

Background

Oral health is an essential component of a healthy pregnancy. While most women work full-time while pregnant, research has overlooked the impact of occupational status and job loss on oral health experiences during pregnancy. To examine the impact of employment status and job loss on oral health experiences during pregnancy in the United States.

Data

Data are from eight sites (Georgia, Massachusetts, Minnesota, Missouri, North Carolina, New York State, New York City, and Wisconsin) of the Pregnancy Risk Assessment Monitoring System (PRAMS) for the years 2016–2020 (n = 31,362). Multiple logistic regression is used to assess the relationship between occupational status (including employment status and unwanted job loss) during pregnancy and oral health.

Findings

Women who experienced an unwanted job loss in the prenatal period were at elevated risk of not having dental insurance, not receiving a dental cleaning during pregnancy, having an oral health problem, and having unmet dental care needs.

Conclusion

Experiencing unwanted job loss around the time of pregnancy is an important life event that corresponds to worse oral health experiences. There is a need for greater focus on adverse life events, such as job loss, especially during pregnancy, as a mechanism for oral health issues and challenges with proper access to dental health systems.
Registered nurses’ challenges and suggestions for improvement of their leadership close to older adults in municipal home healthcare
Authors: Lillsjö Erica , Bjuresäter Kaisa , Josefsson Karin
Published: March 2023

Background

Worldwide people are living longer. The need for healthcare for older adults is increasing. The trend is towards advanced home healthcare, where registered nurses are key figures. This implies challenges for municipal home healthcare, as well as for registered nurses’ leadership. The aim is to explore registered nurses’ perceptions of challenges and suggestions for improvements in their leadership close to older adults in municipal home healthcare.

Methods

The present study is part of a larger web-based questionnaire survey with a cross-sectional design. The design is inductive, analysing data using qualitative content analysis and descriptive statistics. A questionnaire with open-ended and closed-ended questions was used. A total of n = 70 registered nurses leading close to older adults participated in seven municipalities in two geographic areas in Sweden.

Results

The results show registered nurses’ perceptions of challenges as leaders close to older adults in terms of 11 categories. The categories are motivating for care, adjusting and coordinating nursing care to the older adult, relating to next of kin, managing communication difficulties, relating to social situations in the home, managing demands, working alone, having lack of time, collaborating with physicians, and care staff having low competence. The registered nurses suggested improvements for their leadership close to older adults in terms of nine categories. The categories are adjusting the work to the older adult, clarifying registered nurses’ responsibility, balancing demands and resources, setting time aside, improving staffs’ competence, ensuring staff’s competence development, improving the work environment, and cooperation between professions in the municipality, as well as between healthcare organizations.

Conclusion

The results show that registered nurses’ leadership in municipal home healthcare implies a wide range of challenges. There is a need for strategies to improve the organizational preconditions to reduce challenges in registered nurses’ leadership in order to promote positive patient outcomes for safe and quality care.
Longitudinal relationships among career adaptability, resilience, and career commitment in chinese nursing undergraduates: testing differences in career interest between cross-lagged models
Authors: Zhang Jingjing , Zhao Chengjia , Li Feiyue , Wang Xiaoyi , Xu Huihui , Zhou Miaomiao , Huang Yiru , Yang Yeqin , Yu Guoliang , Zhang Guohua
Published: March 2023

Purpose

Various physiological and psychological negative situations experienced by nurses as a result of COVID-19 pandemic have been shown to increase their perception of organizational difficulty and decrease their career commitment, thereby accelerating the turnover rate of nurses. Resilience and career adaptability have important influences on career commitment, so there is a need to evaluate the relationships between them and the underlying mechanisms.

Patients and methods

Using a cross-lagged design, the Career Adaptability Scale, the Chinese version of career commitment, and Davidson’s Resilience Scale as research methods, we studied 692 nursing students for two consecutive years to evaluate the relationship among career adaptability, resilience, and career commitment.

Results

Career adaptability at T1 substantially and positively predicts the career commitment at T2. Career adaptability and resilience are mutually predictive. No interaction is found between resilience and career commitment over time. There is a substantial difference in the cross-lagged relationship among career adaptability, resilience, and career commitment for low- and high-career interest.

Conclusion

Our results show the importance of developing career commitment early on. Developing career adaptability, enhancing resilience, and increasing career interest in nursing students might help to increase career commitment.
Alcohol consumption and microvascular dysfunction: a J-shaped association: The Maastricht Study
Authors: van der Heide Frank C. T. , Eussen Simone J. P. M. , Houben Alfons J. H. M. , Henry Ronald M. A. , Kroon Abraham A. , van der Kallen Carla J. H. , Dagnelie Pieter C. , van Dongen Martien C. J. M. , Berendschot Tos T. J. M. , Schouten Jan S. A. G. , Webers Carroll A. B. , van Greevenbroek Marleen M. J. , Wesselius Anke , Schalkwijk Casper G. , Koster Annemarie , Jansen Jacobus F. A. , Backes Walter H. , Beulens Joline W. J. , Stehouwer Coen D. A.
Published: March 2023

Background

Microvascular dysfunction (MVD) is an important contributor to major clinical disease such as stroke, dementia, depression, retinopathy, and chronic kidney disease. Alcohol consumption may be a determinant of MVD.

Objective

Main objectives were (1) to study whether alcohol consumption was associated with MVD as assessed in the brain, retina, skin, kidney and in the blood; and (2) to investigate whether associations differed by history of cardiovascular disease or sex.

Design

We used cross-sectional data from The Maastricht Study (N = 3,120 participants, 50.9% men, mean age 60 years, and 27.5% with type 2 diabetes [the latter oversampled by design]). We used regression analyses to study the association between total alcohol (per unit and in the categories, i.e. none, light, moderate, high) and MVD, where all measures of MVD were combined into a total MVD composite score (expressed in SD). We adjusted all associations for potential confounders; and tested for interaction by sex, and history of cardiovascular disease. Additionally we tested for interaction with glucose metabolism status.

Results

The association between total alcohol consumption and MVD was non-linear, i.e. J-shaped. Moderate versus light total alcohol consumption was significantly associated with less MVD, after full adjustment (beta [95% confidence interval], -0.10 [-0.19; -0.01]). The shape of the curve differed with sex (Pinteraction = 0.03), history of cardiovascular disease (Pinteraction < 0.001), and glucose metabolism status (Pinteraction = 0.02).

Conclusions

The present cross-sectional, population-based study found evidence that alcohol consumption may have an effect on MVD. Hence, although increasing alcohol consumption cannot be recommended as a policy, this study suggests that prevention of MVD may be possible through dietary interventions.
In vitro activity of rhinacanthin analogues against drug resistant Plasmodium falciparum isolates from Northeast Thailand
Authors: Chaorattanakawee Suwanna , Kosaisavee Varakorn , Bunsermyos Watanyu , Aonsri Chaiyawat , Imaram Witcha , Suwannasin Kanokon , Kunasol Chanon , Thamnurak Chatchadaporn , Boonyalai Nonlawat , Saunders David , Dondorp Arjen M. , Mungthin Mathirut , Imwong Mallika
Published: March 2023

Background

New anti-malarial drugs are needed urgently to address the increasing challenges of drug-resistant falciparum malaria. Two rhinacanthin analogues containing a naphthoquinone moiety resembling atovaquone showed promising in-vitro activity against a P. falciparum laboratory reference strain (K1). The anti-malarial activity of these 2 compounds was further evaluated for P. falciparum field isolates from an area of multi-drug resistance in Northeast Thailand.

Methods

Using a pLDH enzyme-linked immunosorbent assay, four P. falciparum isolates from Northeast Thailand in 2018 were tested for in vitro sensitivity to the two synthetic rhinacanthin analogues 1 and 2 as well as established anti-malarials. Mutations in the P. falciparum cytochrome b gene, a marker for atovaquone (ATQ) resistance, were genotyped in all four field isolates as well as 100 other clinical isolates from the same area using PCR-artificial Restriction Fragment Length Polymorphisms. Pfkelch13 mutations, a marker for artemisinin (ART) resistance, were also examined in all isolates.

Results

The 50% inhibitory concentrations (IC50) of P. falciparum field isolates for rhinacanthin analogue 1 was 321.9–791.1 nM (median = 403.1 nM). Parasites were more sensitive to analogue 2: IC50 48.6–63.3 nM (median = 52.2 nM). Similar results were obtained against P. falciparum reference laboratory strains 3D7 and W2. The ART-resistant IPC-5202 laboratory strain was more sensitive to these compounds with a median IC50 45.9 and 3.3 nM for rhinacanthin analogues 1 and 2, respectively. The ATQ-resistant C2B laboratory strain showed high-grade resistance towards both compounds (IC50 > 15,000 nM), and there was a strong positive correlation between the IC50 values for these compounds and ATQ (r = 0.83–0.97, P < 0.001). There were no P. falciparum cytochrome b mutations observed in the field isolates, indicating that P. falciparum isolates from this area remained ATQ-sensitive. Pfkelch13 mutations and the ring-stage survival assay confirmed that most isolates were resistant to ART.

Conclusions

Two rhinacanthin analogues showed parasiticidal activity against multi-drug resistant P. falciparum isolates, although less potent than ATQ. Rhinacanthin analogue 2 was more potent than analogue 1, and can be a lead compound for further optimization as an anti-malarial in areas with multidrug resistance.
Motor imagery EEG signal classification with a multivariate time series approach
Authors: Velasco I. , Sipols A. , De Blas C. Simon , Pastor L. , Bayona S.
Published: March 2023

Background

Electroencephalogram (EEG) signals record electrical activity on the scalp. Measured signals, especially EEG motor imagery signals, are often inconsistent or distorted, which compromises their classification accuracy. Achieving a reliable classification of motor imagery EEG signals opens the door to possibilities such as the assessment of consciousness, brain computer interfaces or diagnostic tools. We seek a method that works with a reduced number of variables, in order to avoid overfitting and to improve interpretability. This work aims to enhance EEG signal classification accuracy by using methods based on time series analysis. Previous work on this line, usually took a univariate approach, thus losing the possibility to take advantage of the correlation information existing within the time series provided by the different electrodes. To overcome this problem, we propose a multivariate approach that can fully capture the relationships among the different time series included in the EEG data. To perform the multivariate time series analysis, we use a multi-resolution analysis approach based on the discrete wavelet transform, together with a stepwise discriminant that selects the most discriminant variables provided by the discrete wavelet transform analysis

Results

Applying this methodology to EEG data to differentiate between the motor imagery tasks of moving either hands or feet has yielded very good classification results, achieving in some cases up to 100% of accuracy for this 2-class pre-processed dataset. Besides, the fact that these results were achieved using a reduced number of variables (55 out of 22,176) can shed light on the relevance and impact of those variables.

Conclusions

This work has a potentially large impact, as it enables classification of EEG data based on multivariate time series analysis in an interpretable way with high accuracy. The method allows a model with a reduced number of features, facilitating its interpretability and improving overfitting. Future work will extend the application of this classification method to help in diagnosis procedures for detecting brain pathologies and for its use in brain computer interfaces. In addition, the results presented here suggest that this method could be applied to other fields for the successful analysis of multivariate temporal data.
The role and mechanism of action of tRNA-derived fragments in the diagnosis and treatment of malignant tumors
Authors: Gong Mengdan , Deng Yongqin , Xiang Yizhen , Ye Dong
Published: March 2023

Cancer is a leading cause of morbidity and death worldwide. While various factors are established as causing malignant tumors, the mechanisms underlying cancer development remain poorly understood. Early diagnosis and the development of effective treatments for cancer are important research topics. Transfer RNA (tRNA), the most abundant class of RNA molecules in the human transcriptome, participates in both protein synthesis and cellular metabolic processes. tRNA-derived fragments (tRFs) are produced by specific cleavage of pre-tRNA and mature tRNA molecules, which are highly conserved and occur widely in various organisms. tRFs were initially thought to be random products with no physiological function, but have been redefined as novel functional small non-coding RNA molecules that help to regulate RNA stability, modulate translation, and influence target gene expression, as well as other biological processes. There is increasing evidence supporting roles for tRFs in tumorigenesis and cancer development, including the regulation of tumor cell proliferation, invasion, migration, and drug resistance. Understanding the regulatory mechanisms by which tRFs impact these processes has potential to inform malignant tumor diagnosis and treatment. Further, tRFs are expected to become new biological markers for early diagnosis and prognosis prediction in patients with tumors, as well as a targets for precision cancer therapies.
Survival and neurologic outcomes following aortic occlusion for trauma and hemorrhagic shock in a hybrid operating room
Authors: Balch Jeremy A. , Loftus Tyler J. , Efron Philip A. , Mohr Alicia M. , Upchurch Gilbert R. , Smith R. Stephen
Published: March 2023

Background

Outcomes following aortic occlusion for trauma and hemorrhagic shock are poor, leading some to question the clinical utility of aortic occlusion in this setting. This study evaluates neurologically intact survival following resuscitative endovascular balloon occlusion of the aorta (REBOA) versus resuscitative thoracotomy at a center with a dedicated trauma hybrid operating room with angiographic capabilities.

Methods

This retrospective cohort analysis compared patients who underwent zone 1 aortic occlusion via resuscitative thoracotomy (n = 13) versus REBOA (n = 13) for blunt or non-thoracic, penetrating trauma and refractory hemorrhagic shock (systolic blood pressure less than 90 mmHg despite volume resuscitation) at a level 1 trauma center with a dedicated trauma hybrid operating room. The primary outcome was survival to hospital discharge. The secondary outcome was neurologic status at hospital discharge, assessed by Glasgow Coma Scale (GCS) scores.

Results

Overall median age was 40 years, 27% had penetrating injuries, and 23% had pre-hospital closed-chest cardiopulmonary resuscitation. In both cohorts, median injury severity scores and head-abbreviated injury scores were 26 and 2, respectively. The resuscitative thoracotomy cohort had lower systolic blood pressure on arrival (0 [0–75] vs. 76 [65–99], p = 0.009). Hemorrhage control (systolic blood pressure 100 mmHg without ongoing vasopressor or transfusion requirements) was obtained in 77% of all REBOA cases and 8% of all resuscitative thoracotomy cases (p = 0.001). Survival to hospital discharge was greater in the REBOA cohort (54% vs. 8%, p = 0.030), as was discharge with GCS 15 (46% vs. 0%, p = 0.015).

Conclusions

Among patients undergoing aortic occlusion for blunt or non-thoracic, penetrating trauma and refractory hemorrhagic shock at a center with a dedicated, trauma hybrid operating room, nearly half of all patients managed with REBOA had neurologically intact survival. The high death rate in resuscitative thoracotomy and differences in patient cohorts limit direct comparison.
Community participatory learning and action cycle groups to reduce type 2 diabetes in Bangladesh (D:Clare): an updated study protocol for a parallel arm cluster randomised controlled trial
Authors: King Carina , Pires Malini , Ahmed Naveed , Akter Kohenour , Kuddus Abdul , Copas Andrew , Haghparast-Bidgoli Hassan , Morrison Joanna , Nahar Tasmin , Shaha Sanjit Kumer , Khan AKAzad , Azad Kishwar , Fottrell Edward
Published: March 2023

The “Diabetes: Community-led Awareness, Response and Evaluation” (D:Clare) trial aims to scale up and replicate an evidence-based participatory learning and action cycle intervention in Bangladesh, to inform policy on population-level T2DM prevention and control.

The trial was originally designed as a stepped-wedge cluster randomised controlled trial, with the interventions running from March 2020 to September 2022. Twelve clusters were randomly allocated (1:1) to implement the intervention at months 1 or 12 in two steps, and evaluated through three cross-sectional surveys at months 1, 12 and 24. However, due to the COVID-19 pandemic, we suspended project activities on the 20th of March 2020. As a result of the changed risk landscape and the delays introduced by the COVID-19 pandemic, we changed from the stepped-wedge design to a wait-list parallel arm cluster RCT (cRCT) with baseline data. We had four key reasons for eventually agreeing to change designs: equipoise, temporal bias in exposure and outcomes, loss of power and time and funding considerations.

Trial registrationISRCTN42219712. Registered on 31 October 2019.
Leukocyte- and platelet-rich fibrin in cranial surgery: study protocol for a prospective, parallel-group, single-blinded randomized controlled non-inferiority trial {1}
Authors: Coucke Birgit , Van Hoylandt Anaïs , van Loon Johannes , Van Calenbergh Frank , Van Gerven Laura , Theys Tom
Published: March 2023

Background

CSF leakage is a major complication after cranial surgery, thus, adequate dural closure must be performed. Commercially available fibrin sealants are currently considered the gold standard for dural closure, but problems have been reported regarding safety, efficacy, and costs. This trial aims to investigate autologous leukocyte- and platelet-rich fibrin (L-PRF) as an alternative to commercially available fibrin sealants.

Methods/design

This single-blinded, prospective randomized controlled interventional trial aims to demonstrate the non-inferiority of L-PRF compared to commercially available fibrin sealants for dural closure. This trial will include patients undergoing cranial neurosurgery (supratentorial and infratentorial) with intentional opening of the dura. Patients are randomized in a 1:1 fashion comparing L-PRF to commercially available fibrin sealants. The primary endpoint is postoperative CSF leakage within 12 weeks after surgery. Secondary endpoints are complications such as bleeding or wound infections. Additionally, a cost-effectiveness analysis is performed.

Discussion

With this trial, we will evaluate the safety and efficiency of L-PRF compared to commercially available fibrin sealants.

Trial registration

ClinicalTrials.gov NCT03812120. Registered on 22 January 2019.
Enhanced 1,3-propanediol production with high yield from glycerol through a novel Klebsiella–Shewanella co-culture
Authors: Wang Yanxia , Wan Zijian , Zhu Yueting , Hu Haibo , Jiang Yujia , Jiang Wankui , Zhang Wenming , Xin Fengxue
Published: March 2023

Background

1,3-Propanediol (1,3-PDO) is a platform compound, which has been widely used in food, pharmaceutical and cosmetic industries. Compared with chemical methods, the biological synthesis of 1,3-PDO has shown promising applications owing to its mild conditions and environmental friendliness. However, the biological synthesis of 1,3-PDO still has the problem of low titer and yield due to the shortage of reducing powers.

Results

In this study, Klebsiella sp. strain YT7 was successfully isolated, which can synthesize 11.30 g/L of 1,3-PDO from glycerol in flasks. The intracellular redox regulation strategy based on the addition of electron mediators can increase the 1,3-PDO titer to 28.01 g/L. Furthermore, a co-culturing system consisting of strain YT7 and Shewanella oneidensis MR-1 was established, which can eliminate the supplementation of exogenous electron mediators and reduce the by-products accumulation. The 1,3-PDO yield reached 0.44 g/g and the final titer reached 62.90 g/L. The increased titer and yield were attributed to the increased redox levels and the consumption of by-products.

Conclusions

A two-bacterium co-culture system with Klebsiella sp. strain YT7 and S. oneidensis strain MR-1 was established, which realized the substitution of exogenous electron mediators and the reduction of by-product accumulation. Results provided theoretical basis for the high titer of 1,3-PDO production with low by-product concentration.
Therapeutic preference for Alzheimer’s disease treatments: a discrete choice experiment with caregivers and neurologists
Authors: Dranitsaris George , Zhang Quanwu , Mu Lin , Weyrer Christopher , Drysdale Erik , Neumann Peter , Atri Alireza , Monfared Amir Abbas Tahami
Published: March 2023

Background

Alzheimer’s disease (AD) is a major global health crisis in need of more effective therapies. However, difficult choices to optimize value-based care will need to be made. While identifying preferred therapeutic attributes of new AD therapies is necessary, few studies have explored how preferences may vary between the stakeholders. In this study, the trade-offs among key attributes of amyloid plaque-lowering therapies for AD were assessed using a discrete choice experiment (DCE) and compared between caregivers and neurologists.

Methods

An initial pilot study was conducted to identify the potentially relevant features of a new therapy. The DCE evaluated seven drug attributes: clinical effects in terms of delay in AD progression over the standard of care (SOC), variation in clinical effects, biomarker response (achieving amyloid plaque clearance on PET scan), amyloid-related imaging abnormalities-edema (ARIA-E), duration of therapy, need for treatment titration as well as route, and frequency of drug administration. Respondents were then randomly presented with 12 choice sets of treatment options and asked to select their preferred option in each choice set. Hierarchical Bayesian regression modeling was used to estimate weighted preference attributes, which were presented as mean partial utility scores (pUS), with higher scores suggesting an increased preference.

Results

Both caregivers (n = 137) and neurologists (n = 161) considered clinical effects (mean pUS = 0.47 and 0.82) and a 5% incremental in ARIA-E (mean pUS =  − 0.26 and − 0.52) to be highly impactful determinants of therapeutic choice. In contrast, variation in clinical effects (mean pUS = 0.12 and 0.14) and treatment duration (mean pUS =  − 0.02 and − 0.13) were the least important characteristics of any new treatment. Neurologists’ also indicated that subcutaneous drug delivery (mean pUS = 0.42 vs. 0.07) and administration every 4 weeks (mean pUS = 1.0 vs. 0.20) are highly desirable therapeutic features. Respondents were willing to accept up to a 9% increment in ARIA-E for one additional year of delayed progression.

Conclusions

Caregivers and neurologists considered incremental clinical benefit over SOC and safety to be highly desirable qualities for a new drug that could clear amyloid plaques and delay clinical progression and indicated a willingness to accept incremental ARIA-E to achieve additional clinical benefits.
Some new integral inequalities for higher-order strongly exponentially convex functions
Authors: Bisht Jaya , Sharma Nidhi , Mishra Shashi Kant , Hamdi Abdelouahed
Published: March 2023

Integral inequalities with generalized convexity play an important role in both applied and theoretical mathematics. The theory of integral inequalities is currently one of the most rapidly developing areas of mathematics due to its wide range of applications. In this paper, we study the concept of higher-order strongly exponentially convex functions and establish a new Hermite–Hadamard inequality for the class of strongly exponentially convex functions of higher order. Further, we derive some new integral inequalities for Riemann–Liouville fractional integrals via higher-order strongly exponentially convex functions. These findings include several well-known results and newly obtained results as special cases. We believe that the results presented in this paper are novel and will be beneficial in encouraging future research in this field.