bluuebunny/crossref_metadata_2025 huggingface dataset:
Opioid free analgesia after return home in ambulatory colonic surgery patients: a single-center observational study
Authors: Gosgnach Marilyn , Chasserant Philippe , Raux Mathieu
Published: July 2024

Background

Because of the adverse effects of morphine and its derivatives, non-opioid analgesia procedures are proposed after outpatient surgery. Without opioids, the ability to provide quality analgesia after the patient returns home may be questioned. We examined whether an opioid-free strategy could ensure satisfactory analgesia after ambulatory laparoscopic colectomy.

Methods

We performed a retrospective observational single-center study (of prospective collected database) including all patients eligible for scheduled outpatient colectomy. Postoperative analgesia was provided by paracetamol and nefopam. Postoperative follow-up included pain at mobilization (assessed by a numerical rating scale, NRS), hemodynamic variables, temperature, resumption of transit and biological markers of postoperative inflammation. The primary outcome was the proportion of patients with moderate to severe pain (NRS > 4) the day after surgery.

Results

Data from 144 patients were analyzed. The majority were men aged 59 ± 12 years with a mean BMI of 27 [25-30] kg/m2. ASA scores were 1 for 14%, 2 for 59% and 3 for 27% of patients. Forty-seven patients (33%) underwent surgery for cancer, 94 for sigmoiditis (65%) and 3 (2%) for another colonic pathology. Postoperative pain was affected by time since surgery (Q3 = 52.4,p < 0.001) and decreased significantly from day to day. The incidence of moderate to severe pain at mobilization (NRS > 4) on the first day after surgery was (0.19; 95% CI, 0.13–0.27).

Conclusion

Non-opioid analgesia after ambulatory laparoscopic colectomy seems efficient to ensure adequate analgesia. This therapeutic strategy makes it possible to avoid the adverse effects of opioids.

Trial registration

The study was retrospectively registered and approved by the relevant institutional review board (CERAR) reference IRB 00010254–2018 – 188). All patients gave written informed consent for analysis of their data. The anonymous database was declared to the French Data Protection Authority (CNIL) (reference 221 2976 v0 of April 12, 2019).
Development and validation of a prediction nomogram for sleep disorders in hospitalized patients with acute myocardial infarction
Authors: Huang Jing , Li Miao , Zeng Xiu-Wen , Qu Guang-Su , Lin Lu , Xin Xu-Min
Published: July 2024

Purpose

Sleep disorders are becoming more prevalent in hospitalized patients with acute myocardial infarction (AMI). We aimed to investigate the risk factors for sleep disorders in hospitalized patients with AMI, then develop and validate a prediction nomogram for the risk of sleep disorders.

Methods

Clinical data were collected from patients with AMI hospitalized in our hospital from January 2020 to June 2023. All patients were divided into the training group and the validation group with a ratio of 7:3 in sequential order. The LASSO regression analysis and multivariate logistic regression analysis were used to screen potential risk factors for sleep disorders. The concordance index (C-index), calibration curves, and decision curve analysis (DCA) were plotted.

Results

A total of 256 hospitalized patients with AMI were enrolled. Patients were divided into the training group (180) and the validation group (76) according to a scale of 7:3. Of the 256 patients, 90 patients (35.16%) suffered from sleep disorders, and 33 patients (12.89%) needed hypnotics. The variables screened by LASSO regression included age, smoking, NYHA class, anxiety status at admission, depression status at admission, and strangeness of environment. A nomogram model was established by incorporating the risk factors selected. The C-index, calibration curve, and DCA showed good predictive performance.

Conclusions

We identified six clinical characteristics as predictors of sleep disorders in hospitalized patients with AMI. It helps nurses make appropriate decisions in clinical practice.
A novel learner driver first aid eLearning program: a mixed-method pre-post pilot test and evaluation
Authors: Miller Olivia , Newnam Sharon
Published: July 2024

Background

Approximately 1.35 million people worldwide are killed in road accidents every year. Mandatory first aid training for learner drivers has been introduced in some European countries but no such requirements are in effect in Australia. The current study aimed to pilot and evaluate a first aid eLearning program for Australian learner drivers undertaking their mandated supervised driving hours.

Methods

A total of 103 participants (M age = 20.57; 52.4% female, 96% completion rate) responded to an online survey immediately before and two weeks after completing the Learner Driver First Aid program. Participants completed measures of first aid self-efficacy, first aid knowledge, and attitudes towards first aid, and provided qualitative feedback on the program. Paired samples t-tests and Mann-Whitney U tests assessed improvements in first aid self-efficacy, knowledge, and attitudes, and qualitative feedback were analysed thematically.

Results

Participants showed significant pre-post program improvements in first aid self-efficacy (p < .001) and first aid knowledge (p < .001); however, there were no significant changes in attitudes towards first aid (p = .028). Self-efficacy and knowledge improvements were significantly greater for those without prior first aid training (p < .001). Participants rated the usability of the online program favourably and most (93.2%) were satisfied or extremely satisfied with the program. Qualitative feedback suggested participants found the program to be accessible and interactive but noted concerns about the transfer of skills to the real-world context.

Conclusions

The findings provide support for the efficacy of online first aid training for Australian learner drivers. However, further improvements to the eLearning program based on participant feedback should be considered. This study recommends the Learner Driver First Aid program be refined and rolled out to the Australian public.
Influence of the examination position and distension medium on the rectal sensory test in patients with functional constipation
Authors: Xiao Chang-Fang , Li Yi-Fan , Sun Yang-Yang , Meng Ling-Yun , Wu Jing-Wen , Wang Min , Cao Yong-Qing , Wang Chen , Yao Yi-Bo
Published: July 2024

Purpose

To evaluate the impact of two different parameters (body position and distension medium) on the rectal sensory test in patients with functional constipation and provide data support for the development of standardized operating procedures in clinical practice.

Methods

Based on a single-center process of the rectal sensory test, 39 patients with functional constipation were recruited for rectal sensory test under different body positions and distension mediums.

Results

Among the items of the Constipation Scoring System, the score of frequency of bowel movements showed a negative correlation with the first constant sensation volume (r = -0.323, P = 0.045). Conversely, the score of painful evacuation effort showed a positive correlation with the desire to defecate volume (r = 0.343, P = 0.033). There was a statistically significant difference in the first constant sensation volume (when the distension medium was gas) measured in different body positions (left lateral position, sitting position, squatting position), and the data measured in the squatting position were significantly higher than those in left lateral position (P < 0.05). In terms of research on distension medium, it was found that the first constant sensation volume measured in the squatting position (when the distension medium was water) was significantly lower than that of gas (P < 0.05).

Conclusion

For patients with functional constipation, there are differences in the results of rectal sensory tests between body positions and distension mediums. When conducting multicenter studies, it is necessary to unify the standard operating procedure (SOP) for operational details to ensure consistency and reliability of the test results.
Investigating miR-6880-5p in extracellular vesicle from plasma as a prognostic biomarker in endocrine therapy-treated castration-resistant prostate cancer
Authors: Lee Jimin , Hong Jinhwa , Kim Ju Won , Lim Soonyoung , Choi Seung-Cheol , Gim Jeong-An , Kang Sung Gu , Noh Tae Il , Park Kyong Hwa
Published: July 2024

Background

Advancements in the diagnosis, treatment, and surveillance of castration-resistant prostate cancer (CRPC) have progressed considerably, but a new biomarker that combines existing clinical and pathological data could be useful for a more precise diagnosis and prognosis. Some investigations have found that extracellular vesicle (EV)-derived miRNAs play crucial roles in various types of malignant tumors. The objective of this study was to explore EV miRNA and identify its biologic function as a biomarker for the diagnosis and prognosis of CRPC.

Methods

Plasma samples were collected from five healthy donors (Control, CT) and 17 CRPC patients, categorizing into two groups based on their endocrine treatment response: partial response (PR; n = 10) and progressive disease (PD; n = 7). Candidate extracellular vesicle (EV) miRNAs were identified using miRNA microarray and RT-qPCR. The biological functions of the selected miRNAs were evaluated using the MTT assay, wound healing assay, trans-well assay, and RNA sequencing in CRPC cells after transient miRNA expression.

Results

Microarray analysis revealed a significant downregulation of EV-miR-6880-5p in the PD samples compared to both CT and PR samples (p < 0.01). The expression of EV-miR-6880-5p in CRPC patients was decreased compared with that CT group (p = 0.0336) using RT-qPCR. In the PR group, EV-miR-6880-5p was increased at follow-up compared with the baseline (p = 0.2803), while in the PD group, it decreased at follow-up compared with the baseline samples (p = 0.4356). Furthermore, overexpression of miR-6880-5p hampered cell proliferation, migration, and invasion, downregulated pathways associated with tumor progression, and simultaneously upregulated pathways associated with cell growth and apoptosis in CRPC cells.

Conclusions

EV-miR-6880-5p shows promise as a prognostic biomarker in patients with CRPC. Further, prospective validations are necessary to evaluate the potential of these candidate miRNAs.
A phase III, multicentre, randomised, investigator-masked, cross-over, comparative, non-inferiority trial evaluating the efficacy and tolerability of generic preservative-free Latanoprost (Polpharma S.A.) compared to Xalatan® (Pfizer) in patients with ocular hypertension or primary open-angle glaucoma
Authors: Czumbel Norbert , Acs Tamas , Bator Gyorgy , Halmosi Agnes , Egorov Evgeniy A. , Maltsev Dmitrii S.
Published: July 2024

Background

Primary open-angle glaucoma (POAG), often associated with increased intraocular pressure (IOP), can lead to permanent damage of the optic nerve, concomitant visual field loss, and blindness. Latanoprost, a prostaglandin F2α analogue, reduces IOP and is used to treat glaucoma. In this clinical trial, we evaluated the efficacy of Latanoprost Polpharma, a generic preservative-free latanoprost 0.05 mg/ml eye drops solution, in lowering IOP when compared to the originator Xalatan® (latanoprost 0.005% ophthalmic solution, Pfizer).

Methods

This was a Phase III, multicentre, randomized, investigator-masked, cross-over, comparative, non-inferiority trial carried out in 5 sites in Hungary and Russia. The primary endpoint was to evaluate the non-inferiority of the test product when compared to the reference product with respect to the differences in the mean diurnal IOP on Day 1 (baseline) and Day 29. The secondary endpoints included efficacy, ocular tolerance, safety, and usability. We recruited adult patients (18–75 years) with open-angle glaucoma or ocular hypertension.

Results

Forty-nine patients were randomised and received at least one dose of the test or reference product. A virtually identical reduction of the mean diurnal IOP of 7.04 ± 2.14 mmHg or 7.17 ± 2.11 mmHg was found after treatment with test or reference product, respectively (N = 44). In the intention to treat analysis, the reduction was 7.29 ± 2.53 mmHg (95% CI: 6.55–8.04) or 7.43 ± 2.78 mm Hg (95%CI: 6.61–8.24) after treatment with test or reference product, respectively (N = 47). There were no serious adverse events.

Conclusions

Latanoprost Polpharma was shown to be non-inferior to Xalatan®. Both investigational products were equally well tolerated and safe. The data show a trend in favour of the test product with regards to the severity of hyperaemia and to the velocity of remission of ocular discomfort. Latanoprost Polpharma, being preservative-free, also avoids the cytotoxicity of benzalkonium chloride, the side effects of which may affect patient compliance and lower the quality of life.

Trial registration

The study had the ethical and regulatory approval from the National Institute of Pharmacy and Nutrition (OGYEI, OGYEI/41,779- 11/2018) and the Ethics Committee for Clinical Pharmacology (KFEB) of Hungary and from the Ministry of Healthcare of the Russian Federation (MOH of Russia) prior to the beginning of the study (642/25.12.2018) (clinical trial identification number: 848,300,144/0103/1 - POP03; IND number/EudraCT number: 2018-001727-39).
Trends in diabetic ketoacidosis in Victoria, Australia 2002–2016
Authors: Jones Hanna C. , Kiburg Katerina V. , Lee Melissa H. , O’Neal David N. , MacIsaac Richard J.
Published: July 2024

Background

International longitudinal studies have indicated an increasing incidence of diabetic ketoacidosis (DKA). We aim to examine the incident trends, demographic differences, length of stay and mortality for DKA in adults with type 1 diabetes (T1D) and type 2 diabetes (T2D) in Victoria, Australia from 2002 to 2016.

Methods

Age and sex adjusted incident trends, length of stay and mortality for DKA was retrospectively obtained using the Victorian Admitted Episode Dataset between 2002 and 2016. Data for adults with T1D and T2D was obtained from the National Diabetes Services Scheme (NDSS). Joinpoint regression analysis was used to identify changes in linear trends that were described as average annual percentage change (AAPC).

Results

There were 23,628 DKA presentations in Victoria between 2002 and 2016. For T1D there was an increase in DKA presentations (AAPC + 6.8%) from 2003 to 2016 and for T2D there was a decline from 2003 to 2011 (APC − 3.5%), increase from 2011 to 2014 (APC + 38.5%), and a decrease from 2014 to 2016 (APC − 20.9%). Length of stay was longer for people with T2D than T1D (P < 0.001) and the mortality rate was 0.51% for the study period.

Conclusions

DKA rates increased for T2D from 2011 to 2014 which correlates with the introduction of sodium glucose-linked transport protein 2 inhibitors. However, the aetiology for the observed increase in T1D from 2002 to 2016 remains unknown.
Sexual health—a topic for cancer patients receiving oncological treatment with palliative intent
Authors: Schmalz Claudia , Oberguggenberger Anne S. , Nagele Eva , Bliem Brigitte , Lanceley Anne , Nordin Andy , Kuljanic Karin , Jensen Pernille T. , Bjelic-Radisic Vesna , Fabian Alexander , Arraras Juan I. , Wei-Chu Chie , Creutzberg Carien L. , Galalae Razvan , Toelen Hilde , Zimmermann Kristin , Costantini Anna , Almont Thierry , Serpentini Samantha , Frøding Ligita Paskeviciute , Vistad Ingvild , Tomaszewski Krzysztof A. , Inwald Elisabeth , Greimel Elfriede ,   the EORTC Quality of Life Group
Published: July 2024

Objectives

Sexuality is an important dimension of health-related quality of life (HRQOL) in cancer patients. Studies evidence that most patients report impairments of their sexual health related to their disease or its treatment. The Quality of Life Group of the European Organization for the Research and Treatment of Cancer (EORTC) developed a patient reported outcome measure assessing multidimensional aspects of sexual health. The validation study for this instrument revealed heterogenous results for patients in palliative oncological treatment. The aim of this secondary analyses is to examine differences in patient related sexual health outcomes between palliative patients with good performance status (GPS) and those with poor performance status (PPS).

Methods

In this observational cohort study, self-reported sexual health issue scores were compared between the two groups of patients in palliative oncological treatment with GPS vs PPS status.

Results

Patients with GPS experienced significantly more sexual satisfaction than patients with PPS (p = 0.015). They reported significantly more treatment effects on their sexual activity (p = 0.005) and suffer more from decreased libido (p = 0.008). Patients with PPS reported significantly more fatigue (p = 0.03) and regarded preservation of sexual activity of higher importance than did patients with GPS (p = 0.049).

Conclusions

Our study demonstrates the importance of sexuality for patients in palliative oncological treatment, especially for those with limited performance status. Considering the patients´ perspective, sexual health reaches beyond physical functioning. Patients in a palliative phase of disease report high levels of psychosexual problems while sexual performance deteriorates. Sexuality is an important aspect of HRQOL for these patients, needs to be addressed by health care providers and sensitively integrated into palliative care plans.
Development of an admission criterion framework for high-cost medical consumables in governmental hospitals: a systematic review
Authors: Chu Tianshu , Han Yahui , Wang Haiyin
Published: July 2024

Background

High-cost medical consumables (HMCs) have emerged as significant economic and technological challenges for numerous national healthcare systems. Governmental hospitals play an indispensable role in many national health systems, closely linked to the evaluation of admissions and the management of procurement for HMCs. Nevertheless, many governmental hospitals face avoidable management risks due to the lack of a decision-making tool. In response, we conducted a systematic review to establishing a framework for the admission criteria of HMCs. This framework aims to enhance their effective utilization and maximize economic, clinical, and social benefits.

Methods

In accordance with a systematic review protocol developed for our study, we conducted comprehensive searches in the PubMed, Web of Science, and Embase databases to identify all correlation studies conducted prior to December 31, 2021. Subsequently, two independent reviewers performed a two-round screening process, resulting in the inclusion of 23 articles in our study. Finally, a third reviewer meticulously examined the selected indicators and contributed to the development of the final criterion framework.

Results

The criterion framework was established with 7 first-level indicators and 23 s-level indicators. Among the first-level indicators, "Clinical Benefit" held the highest significance, with a combined weight of 1.606, followed by "Economic Value" and "Organizational Impact" at 1.497 and 1.159, respectively. At the second level, "Safety" and "Efficacy" carried equal weight in the decision-making tool, with combined weights of approximately 1.300 each and a standard combined weight of 0.130.

Conclusion

This admission criteria framework serves as a vital decision-making tool for managing admissions and highlights several crucial evaluation indicators. Economic considerations emerge as the principal determinant in HMCs procurement decisions. Consequently, healthcare managers and decision-makers are recommended to give precedence to value-based healthcare and evidence-based procurement practices. In the long term, governmental hospitals must grapple with the challenge of judiciously allocating limited resources to maximize both social and economic benefits.
An original study assessing biomarker success rate in breast cancer recurrence biomarker research
Authors: Savva K-V. , MacKenzie A. , Coombes R. C. , Zhifang N. M. , Hanna B. G. , Peters C. J.
Published: July 2024

Background

Breast cancer is the second most common cause of cancer mortality worldwide. Biomarker discovery has led to advances in understanding molecular phenotyping and thus has a great potential for precision management of this diverse disease. Despite increased interest in the biomarker field, only a small number of breast cancer biomarkers are known to be clinically useful. Therefore, it is very important to characterise the success rate of biomarkers in this field and study potential reasons for the deficit. We therefore aim to achieve quantitative characterisation of the biomarker translation gap by tracking the progress of prognostic biomarkers associated with breast cancer recurrence.

Methods

An electronic systematic search was conducted in Medline and Embase databases using keywords and mesh headings associated with breast cancer recurrence biomarkers (1940–2023). Abstracts were screened, and primary clinical studies involving breast cancer recurrence biomarkers were selected. Upon identification of relevant literature, we extracted the biomarker name, date of publication and journal name. All analyses were performed using IBM SPSS Statistics and GraphPad prism (La Jolla, California, USA).

Results

A total of 19,195 articles were identified, from which 4597 articles reported breast cancer biomarkers associated with recurrence. Upon data extraction, 2437 individual biomarkers were identified. Out of these, 23 are currently recommended for clinical use, which corresponds to only 0.94% of all discovered biomarkers.

Conclusions

This study characterised for the first time the translational gap in the field of recurrence-related breast cancer biomarkers, indicating that only 0.94% of identified biomarkers were recommended for clinical use. This denotes an evident barrier in the biomarker research field and emphasises the need for a clearer route from biomarker discovery through to implementation.
Wound healing induced by new synthetic peptide, A7-1, in C57BL/6 mouse model
Authors: Jung Gyu Sik , Park Taehwan , Ryu JeongYeop , Lee Joon Seok , Yang Jung Dug , Chung Ho Yun , Choi Kang Young
Published: July 2024

The effects of the novel synthetic peptide, A7-1, on wound healing and skin grafts were evaluated in a C57BL/6 mouse model. Two 15-mm wide circular skin excisions were made on the backs of mice and to each excision, 100 µM A7-1 or normal saline was applied daily. The treatments were applied and sutured for skin graft analysis. Digital photos were acquired on days 4, 7, 11, and 14 and fluorescein angiography was conducted. Wound sizes were verified using stereoscopic microscopy. Histological analysis was performed via hematoxylin and eosin staining and Masson’s trichrome staining. Western blotting was performed using vascular endothelial growth factor. Using a stereoscopic microscope, significantly faster wound healing (17.3%) and skin graft healing (16.5%) were observed in the A7-1 treatment group in comparison to that of the control. The angiogenesis was significantly faster in fluorescein angiography examination in wound healing (11%) and skin grafts (15%). However, the average completion of epithelization (overall time for wound healing), did not show any significant differences. In comparison to the control, the new protein, A7-1, led to significantly faster wound healing in the initial angiogenesis.
Axillary management and long-term oncologic outcomes in breast cancer patients with clinical N1 disease treated with neoadjuvant chemotherapy
Authors: Sparger Courtney C. , Hernandez Alexandra E. , Rojas Kristin E. , Khan Khadeja , Halfteck Gili G. , Möller Mecker , Avisar Eli , Goel Neha , Crystal Jessica S. , Kesmodel Susan B.
Published: July 2024

Background

Low false negative rates can be achieved with sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients with clinical N1 (cN1) disease. We examined changes in axillary management and oncologic outcomes in BC patients with cN1 disease receiving NAC.

Methods

BC patients with biopsy proven cN1 disease treated with NAC were selected from our institutional cancer registry (2014–2017). Patients were grouped by axillary management, axillary lymph node dissection (ALND), SLNB followed by ALND, or SLNB alone. Univariable and multivariable survival analysis for recurrence-free survival (RFS) and overall survival (OS) were performed.

Results

81 patients met inclusion criteria: 31 (38%) underwent ALND, 25 (31%) SLNB + ALND, and 25 (31%) SLNB alone. A SLN was identified in 45/50 (90%) patients who had SLNB. ALND was performed in 25/50 (50%) patients who had SLNB: 18 for a + SLNB, 5 failed SLNB, and 2 insufficient SLNs. 25 patients had SLNB alone, 17 were SLN- and 8 SLN+. In the SLNB alone group, 23/25 (92%) patients received adjuvant radiation (RT). 20 (25%) patients developed BC recurrence: 14 distant (70%), 3 local (15%), 2 regional + distant (10%), and 1 contralateral (5%). In the SLNB alone group, there was 1 axillary recurrence in a patient with a negative SLNB who did not receive RT. Univariable survival analysis showed significant differences in RFS and OS between axillary management groups, ALND/SLNB + ALND vs. SLNB alone (RFS: p = 0.006, OS: p = 0.021). On multivariable survival analysis, worse RFS and OS were observed in patients with TNBC (RFS: HR 3.77, 95% CI 1.70–11.90, p = 0.023; OS: HR 8.10, 95% CI 1.84–35.60, p = 0.006).

Conclusions

SLNB alone and RT after NAC in BC patients with cN1 disease who have negative SLNs at surgery provides long-term regional disease control. This analysis provides support for the practice of axillary downstaging with NAC and SLNB alone.
Revisiting the concept of bout: associations of moderate-to-vigorous physical activity sessions and non-sessions with mortality
Authors: Ma Tongyu , Sirard John , Yang Lin , Li Ye , Tsang Sharon , Fu Amy
Published: July 2024

Introduction

Current physical activity guidelines recommend 150 min of moderate-to-vigorous physical activity (MVPA) for health benefits, regardless of the pattern of MVPA. However, MVPA that occurs in sessions (MVPA-S) may have different health implications compared to MVPA that is not accumulated in sessions (MVPA-nonS). This study aimed to investigate the associations of MVPA-S and MVPA-nonS with mortality.

Methods

We conducted a cohort study of the National Health and Nutrition Examination Survey 2003–2006 (n = 5,658) with accelerometer-measured physical activity at baseline and mortality followed through December 31, 2019. A session was defined as a time window of 30 min or longer where the average intensity was at or above 2020 counts/minute. MVPA accumulated within such sessions was quantified as MVPA-S, while MVPA accumulated outside the sessions was quantified as MVPA-nonS. We examined the joint association of MVPA-S and MVPA-nonS by classifying the participants into four groups (both < 75 min/week [referent], MVPA-S ≥ 75 and MVPA-nonS < 75, MVPA-S < 75 and MVPA-nonS ≥ 75, and both ≥ 75). We used 75 min as the cut-point because it is half of the guideline-recommended MVPA volume where a strong MVPA-mortality association has been observed in previous studies, and because it was close to the median of MVPA-nonS (75 min/week was the 54th percentile), allowing a sufficient sample size in each group for testing statistical significance. The hazard ratios and 95% confidence intervals were estimated with adjustment for important confounders.

Results

During 13.9 years of follow-up (74,988 person-years), there were 1,424 deaths, out of which 472 were related to cardiovascular diseases (CVD). Compared to the referent combination (both < 75), the hazard ratios in the other three combinations were 0.48 (0.33–0.69), 0.85 (0.71–1.01), and 0.45 (0.30–0.67) for all-cause mortality; and were 0.34 (0.17–0.70), 0.96 (0.69–1.33), and 0.40 (0.17–0.90) for CVD mortality, respectively. Results were largely consistent in the spline-based models, age- and sex-stratified analyses, complete-case analysis, competing risk analysis, and the analysis excluding deaths within two years of follow-up.

Conclusion

In conclusion, MVPA accumulated in sessions that lasted at least 30 min was associated with significant reductions in all-cause and CVD-specific mortality risks. The health implications of MVPA that were not accumulated in such sessions warrant further investigation.
PHF12 regulates HDAC1 to promote tumorigenesis via EGFR/AKT signaling pathway in non-small cell lung cancer
Authors: Kong Yiru , Jiang Rongrong , Zhou Hui , Ge Mengxi , Lin Hao , Wang Yu , Yao Rongrong , Wang Qing , Liang Xiaohua , Li Jing , Zhou Xinli
Published: July 2024

Background

Lung cancer stands as the second most prevalent malignant neoplasm worldwide. Addressing the underlying mechanisms propelling the progression of non-small cell lung cancer is of paramount importance. In this study, we have elucidated the pivotal role of PHF12 in this context.

Materials and methods

We harnessed clinical lung cancer tissue samples and non-small cell lung cancer cell lines to discern the expression pattern of PHF12. In vitro assays probing cell proliferation were conducted to substantiate the functional impact of PHF12. Furthermore, an in vivo Xenograft model was employed to dissect the role of PHF12. Employing ChIP assays and qRT-PCR, we delved into the intricate binding dynamics between PHF12 and HDAC1. Mechanistic insights into the PHF12-HDAC1 axis in lung cancer progression were pursued via RNA-seq and GSEA analyses.

Results

Notably, PHF12 exhibited a substantial upregulation within tumor tissue, concomitant with its correlation to HDAC1. The trilogy of cell proliferation assays, transwell assays, and the Xenograft model collectively underscored the promoting influence of PHF12 on lung cancer proliferation, both in vitro and in vivo. The ChIP assay unveiled the transcriptional regulatory role of PHF12 in governing HDAC1 expression. This correlation extended to both mRNA and protein levels. PHF12 promotes NSCLC progression through regulating HDCA1 expression. Intriguingly, the rescue of function within NSCLC cell lines post PHF12 knockdown was achievable through HDAC1 overexpression. Additionally, our findings unveiled the capacity of the PHF12-HDAC1 axis to activate the EGFR/AKT signaling pathway, thereby further corroborating its significance in lung cancer progression.

Conclusion

Our study identified PHF12 as an oncogenic role in lung cancer proliferation and migration for the first time. PHF12 transcriptionally regulate HDAC1 and activate EGFR/AKT signaling pathway in NSCLC progression. PHF12 may serve as an important target in lung cancer therapy.
Helicobacter pylori infection exacerbates metabolic dysfunction-associated steatotic liver disease through lipid metabolic pathways: a transcriptomic study
Authors: Chen Xingcen , Peng Ruyi , Peng Dongzi , Liu Deliang , Li Rong
Published: July 2024

Background

The relationship between Helicobacter pylori (H. pylori) infection and metabolic dysfunction-associated steatotic liver disease (MASLD) has attracted increased clinical attention. However, most of those current studies involve cross-sectional studies and meta-analyses, and experimental mechanistic exploration still needs to be improved. This study aimed to investigate the mechanisms by which H. pylori impacts MASLD.

Methods

We established two H. pylori-infected (Cag A positive and Cag A negative) mouse models with 16 weeks of chow diet (CD) or high-fat diet (HFD) feeding. Body weight, liver triglyceride, blood glucose, serum biochemical parameters, inflammatory factors, and insulin resistance were measured, and histological analysis of liver tissues was performed. Mouse livers were subjected to transcriptome RNA sequencing analysis.

Results

Although H. pylori infection could not significantly affect serum inflammatory factor levels and serum biochemical parameters in mice, serum insulin and homeostatic model assessment for insulin resistance levels increased in CD mode. In contrast, H. pylori Cag A + infection significantly aggravated hepatic pathological steatosis induced by HFD and elevated serum inflammatory factors and lipid metabolism parameters. Hepatic transcriptomic analysis in the CD groups revealed 767 differentially expressed genes (DEGs) in the H. pylori Cag A + infected group and 1473 DEGs in the H. pylori Cag A- infected group, and the “nonalcoholic fatty liver disease” pathway was significantly enriched in KEGG analysis. There were 578 DEGs in H. pylori Cag A + infection combined with the HFD feeding group and 820 DEGs in the H. pylori Cag A- infected group. DEGs in the HFD groups were significantly enriched in “fatty acid degradation” and “PPAR pathway.” Exploring the effect of different Cag A statuses on mouse liver revealed that fatty acid binding protein 5 was differentially expressed in Cag A- H. pylori. DEG enrichment pathways were concentrated in the “PPAR pathway” and “fatty acid degradation.”

Conclusions

Clinicians are expected to comprehend the impact of H. pylori on MASLD and better understand and manage MASLD. H. pylori infection may exacerbate the development of MASLD by regulating hepatic lipid metabolism, and the H. pylori virulence factor Cag A plays a vital role in this regulation.
Inflammatory damage caused by Echovirus 30 in the suckling mouse brain and HMC3 cells
Authors: Li Jichen , Zong Yanjun , Sun Tiantian , Liu Ying , Wang Rui , Zhou Jianfang , Sun Qiang , Zhang Yong
Published: July 2024

Echovirus 30 (E30), a member of the species B Enterovirus family, is a primary pathogen responsible for aseptic meningitis and encephalitis. E30 is associated with severe nervous system diseases and is a primary cause of child illness, disability, and even mortality. However, the mechanisms underlying E30-induced brain injury remain poorly understood. In this study, we used a neonatal mouse model of E30 to investigate the possible mechanisms of brain injury. E30 infection triggered the activation of microglia in the mouse brain and efficiently replicated within HMC3 cells. Subsequent transcriptomic analysis revealed inflammatory activation of microglia in response to E30 infection. We also detected a significant upregulation of polo-like kinase 1 (PLK1) and found that its inhibition could limit E30 infection in a sucking mouse model. Collectively, E30 infection led to brain injury in a neonatal mouse model, which may be related to excessive inflammatory responses. Our findings highlight the intricate interplay between E30 infection and neurological damage, providing crucial insights that could guide the development of interventions and strategies to address the severe clinical manifestations associated with this pathogen.
Cost-effectiveness of train-the-trainer versus expert consultation training models for implementing interpersonal psychotherapy in college mental health settings: evidence from a national cluster randomized trial
Authors: Raghavan Ramesh , Fitzsimmons-Craft Ellen E. , Welch R. Robinson , Jo Booil , Proctor Enola K. , Wilson G. Terence , Agras W. Stewart , Wilfley Denise E.
Published: July 2024

Background

This study is a cost-effectiveness study of two implementation strategies designed to train therapists in college and university counseling centers to deliver interpersonal psychotherapy. Costs of implementing a train-the-trainer (TTT) strategy versus an expert consultation strategy were estimated, and their relative effects upon therapist outcomes were calculated and compared.

Methods

Twenty four counseling centers were recruited across the United States. These centers were randomized to either a TTT (experimental) condition, in which an in-house therapist trained other center therapists, or an expert consultation condition, in which center therapists participated in a workshop and received 12 months of ongoing supervision. The main outcome was therapist fidelity (adherence and competence) to interpersonal psychotherapy, assessed via audio recordings of therapy sessions, and analyzed using linear mixed models. Costs of each condition were quantified using time-driven activity-based costing methods, and involved a costing survey administered to center directors, follow up interviews and validation checks, and comparison of time tracking logs of trainers in the expert condition. Mean costs to produce one therapist were obtained for each condition. The costs to produce equivalent improvements in therapist-level outcomes were then compared between the two conditions.

Results

Mean cost incurred by counseling centers to train one therapist using the TTT strategy was $3,407 (median = $3,077); mean cost to produce one trained therapist in the control condition was $2,055 (median = $1,932). Therapists in the TTT condition, on average, demonstrated a 0.043 higher adherence score compared to therapists in the control condition; however, this difference was not statistically significant. For the competence outcome, effect size for therapists in the TTT condition was in the large range (1.16; 95% CI: 0.85–1.46; p < .001), and therapists in this condition, on average, demonstrated a 0.073 higher competence score compared to those in the expert consultation condition (95% CI, 0.008–0.14; p = .03). Counseling centers that used the TTT model incurred $353 less in training costs to produce equivalent improvements in therapist competence.

Conclusions

Despite its higher short run costs, the TTT implementation strategy produces greater increases in therapist competence when compared to expert consultation. Expanding resources to support this platform for service delivery can be an effective way to enhance the mental health care of young people seeking care in college and university counseling centers.

Trial registration

ClinicalTrials.gov Identifier: NCT02079142.
Developing a nomogram for predicting acute complicated course in pediatric acute hematogenous osteomyelitis
Authors: Zhao Chaochen , Jiang Qizhi , Wu Wangqiang , Shen Yiming , Zhu Yujie , Wang Xiaodong
Published: July 2024

Background

The objective of this study was to develop and validate a nomogram for predicting the risk of an acute complicated course in pediatric patients with Acute Hematogenous Osteomyelitis (AHO).

Methods

A predictive model was developed based on a dataset of 82 pediatric AHO patients. Clinical data, imaging findings, and laboratory results were systematically collected for all patients. Subsequently, biomarker indices were calculated based on the laboratory results to facilitate a comprehensive evaluation. Univariate and multivariate logistic regression analyses were conducted to identify factors influencing early adverse outcomes in AHO. A nomogram model was constructed based on independent factors and validated internally through bootstrap methods. The discriminative ability, calibration, and clinical utility of the nomogram model were assessed using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA), respectively. The developed nomogram model was compared with previously published A-score and Gouveia scoring systems.

Results

Logistic regression analysis identified delayed source control, suppurative arthritis, albumin on admission, and platelet to lymphocyte ratio (PLR) as independent predictors of early adverse outcomes in pediatric AHO patients. The logistic regression model was formulated as: Log(P) = 7. 667–1.752 × delayed source control − 1.956 × suppurative arthritis − 0.154 × albumin on admission + 0.009 × PLR. The nomogram’s AUC obtained through Bootstrap validation was 0.829 (95% CI: 0.740–0.918). Calibration plots showed good agreement between predictions and observations. Decision curve analysis demonstrated that the model achieved net benefits across all threshold probabilities. The predictive efficacy of our nomogram model for acute complicated course in pediatric AHO patients surpassed that of the A-score and Gouveia scores.

Conclusions

A predictive model for the acute complicated course of pediatric AHO was established based on four variables: delayed source control, suppurative arthritis, albumin on admission, and PLR. This model is practical, easy to use for clinicians, and can aid in guiding clinical treatment decisions.
RETRACTED ARTICLE: Early or delayed cord clamping during transition of term newborns: does it make any difference in cerebral tissue oxygenation?
Authors: Arcagok Baran Cengiz , Bilgen Hulya , Ozdemir Hulya , Memisoglu Asli , Save Dilsad , Ozek Eren
Published: July 2024

Background

According to the World Health Organization’s recommendation,
delayed cord clamping in term newborns can have various benefits. Cochrane
metaanalyses reported no differences for mortality and early neonatal morbidity
although a limited number of studies investigated long-term neurodevelopmental
outcomes. The aim of our study is to compare the postnatal cerebral tissue
oxygenation values in babies with early versus delayed cord clamping born after
elective cesarean section.

Methods

In this study, a total of 80 term newborns delivered by elective
cesarean section were included. Infants were randomly grouped as early (clamped
within 15 s, n:40) and delayed cord clamping (at the 60th second, n:40)
groups. Peripheral arterial oxygen saturation (SpO2) and heart rate were
measured by pulse oximetry while regional oxygen saturation of the brain (rSO2)
was measured with near-infrared spectrometer. Fractional tissue oxygen
extraction (FTOE) was calculated for every minute between the 3rd and 15th
minute after birth. (FTOE = pulse oximetry value-rSO2/pulse
oximetry value). The measurements were compared for both groups.

Results

The demographical characteristics, SpO2 levels (except postnatal
6th, 8th, and 14th minutes favoring DCC p < 0.05), heart rates and umbilical cord blood
gas values were not significantly different between the groups (p > 0.05). rSO2 values were
significantly higher while FTOE values were significantly lower for every minute
between the 3rd and 15th minutes after birth in the delayed cord clamping group
(p < 0.05).

Conclusion

Our study revealed a significant increase in cerebral rsO2 values
and a decrease in FTOE values in the delayed cord clamping (DCC) group,
indicating a positive impact on cerebral oxygenation and hemodynamics.
Furthermore, the DCC group exhibited a higher proportion of infants with
cerebral rSO2 levels above the 90th percentile. This higher proportion, along
with a lower of those with such parameter below the 10th percentile, suggest
that DCC may lead to the targeted/optimal cerebral oxygenetaion of these babies.
As a result, we recommend measuring cerebral oxygenation, in addition to
peripheral SpO2, for infants experiencing perinatal hypoxia and receiving
supplemental oxygen.
Mining alternative splicing patterns in scRNA-seq data using scASfind
Authors: Song Yuyao , Parada Guillermo , Lee Jimmy Tsz Hang , Hemberg Martin
Published: July 2024

Single-cell RNA-seq (scRNA-seq) is widely used for transcriptome profiling, but most analyses focus on gene-level events, with less attention devoted to alternative splicing. Here, we present scASfind, a novel computational method to allow for quantitative analysis of cell type-specific splicing events using full-length scRNA-seq data. ScASfind utilizes an efficient data structure to store the percent spliced-in value for each splicing event. This makes it possible to exhaustively search for patterns among all differential splicing events, allowing us to identify marker events, mutually exclusive events, and events involving large blocks of exons that are specific to one or more cell types.
Commentary: The North West London Clinical Trials Alliance: efficiency and innovation in clinical trial delivery
Authors: Kierkegaard Patrick , Su Bowen , Wong Richard , Boffito Marta , Balendra Suki
Published: July 2024

Background

The set-up, activation, and delivery of clinical trials is pivotal for the advancement of medical science, serving as the primary mechanism through which new therapeutic interventions are validated for clinical use. Despite their critical role, the execution of these trials is often encumbered by a multitude of challenges. The North West London Clinical Trials Alliance (The Alliance) was established to address these complexities. It aims to bridge the gap between emerging scientific research and its clinical application through strategic collaborations among healthcare and research entities, thereby enhancing the regional ecosystem for clinical trials.

Main text

This commentary aims to offer clarity on the fundamental insights that underlie The Alliance, providing a comprehensive understanding of its operational structure and the ecosystem it has fostered to optimise clinical trial delivery and revenue generation. The strategy employed by The Alliance centres on the cultivation of strategic partnerships across a broad spectrum of stakeholders. This approach addresses key operational challenges in clinical trial management, facilitating improvements in the development, setup, activation, and recruitment stages. Notably, The Alliance has reduced the average time to initiate trials to 19 days, compared to the standard 75 days typically observed for commercial setups in North West London. The effectiveness of The Alliance’s framework was notably demonstrated during the COVID-19 pandemic, particularly with the expedited recruitment performance in the Janssen COVID-19 vaccine study conducted at Charing Cross Hospital. This instance highlighted the Alliance’s capability to meet and exceed recruitment targets promptly while maintaining diversity within study cohorts. Additionally, The Alliance has effectively harnessed digital technology and infrastructure, enhancing its attractiveness to commercially funded studies and illustrating a sustainable model for clinical trial financing and execution.

Conclusion

The North West London Clinical Trials Alliance represents a strategic response to the conventional challenges faced in clinical trial management, emphasising the importance of cross-sectoral collaboration and resource optimisation. Its efforts, particularly highlighted by its response to the COVID-19 pandemic, provide a case study in enhancing trial delivery and efficiency with significant implications for both regional and global clinical trials research communities.