bluuebunny/crossref_metadata_2025 huggingface dataset:
U-Net deep learning model for endoscopic diagnosis of chronic atrophic gastritis and operative link for gastritis assessment staging: a prospective nested case–control study
Authors: Zhao Quchuan , Jia Qing , Chi Tianyu
Published: November 2023

Background:

The operative link for the gastritis assessment (OLGA) system can objectively reflect the stratification of gastric cancer risk in patients with chronic atrophic gastritis (CAG).

Objectives:

We developed a real-time video monitoring model for the endoscopic diagnosis of CAG and OLGA staging based on U-Net deep learning (DL). To further validate and improve its performance, we designed a study to evaluate the diagnostic evaluation indices.

Design:

A prospective nested case–control study

Methods:

Our cohort consisted of 1306 patients from 31 July 2021 to 31 January 2022. According to the pathological results, patients in the cohort were divided into the CAG group and the chronic non-atrophic gastritis group to evaluate the diagnostic evaluation indices. Each atrophy lesion was automatically labeled and the atrophy severity was assessed by the model. Propensity score matching was used to minimize selection bias.

Results:

The diagnostic evaluation indices and the consistency between OLGA staging and pathological diagnosis of the model were superior to those of endoscopists [sensitivity (89.31% versus 67.56%), specificity (90.46% versus 70.23%), positive predictive value (90.35% versus 69.41%), negative predictive value (89.43% versus 68.40%), accuracy rate (89.89% versus 68.89%), Youden index (79.77% versus 37.79%), odd product (79.23 versus 4.91), positive likelihood ratio (9.36 versus 2.27), negative likelihood ratio (0.12 versus 0.46)], areas under the curves (AUC) (95% CI) (0.919 (0.893–0.945) versus 0.749 (0.707–0.792), p < 0.001) and kappa (0.816 versus 0.291)].

Conclusion:

Our study demonstrated that the DL model can assist endoscopists in real-time diagnosis of CAG during gastroscopy and synchronous identification of high-risk OLGA stage (OLGA stages III and IV) patients.

Trial registration:

ChiCTR2100044458.
Updating proxy-based site amplification map with in-situ data in Osaka, Japan: A Bayesian scheme based on uncertainty projected mapping
Authors: Chakraborty Anirban , Goto Hiroyuki , Sawada Sumio
Published: November 2023

Site amplification maps are mostly proxy-based. Often due to the absence of in-situ data at the regional or local scale, a high level of confidence cannot be assigned to the site amplifications. It has often been observed that the in-situ amplifications differ from proxy-based estimates. So, whenever new in-situ data are made available, it is necessary to update the proxy-based estimates. Bayesian frameworks are recently gaining attention as model updating schemes. This study proposes a Bayesian scheme for updating proxy-based maps with in-situ data. This scheme is based on uncertainty projected mapping (UPM), where the significance of local in-situ data variability determines the posterior estimates. The study area is in Osaka, Japan, where discrepancies in proxy-based estimates and observed ground motions were documented during the 2018 Northern Osaka earthquake. Dense borehole data from the Kansai Geo-informatics Network are available in this area. Peak ground velocity (PGV) site amplification evaluations from this dense borehole network are used as likelihoods to update the prior proxy-based Japan seismic hazard information system (J-SHIS) site amplification map. As a result, the posterior map shows updated site amplification estimates which better represent the in-situ data. The updated site amplification map is then used to investigate the role of site amplification in explaining the building damage during the 2018 Northern Osaka earthquake.
Factors for delays in door-to-balloon time ≤ 90 min in an electrocardiogram triage system among patients with ST-segment elevation myocardial infarction: a retrospective study
Authors: Inoue Atsuhito , Mizobe Michiko , Takahashi Jin , Funakoshi Hiraku
Published: November 2023

Background

Door to balloon time is a crucial factor of mortality in patients with ST-segment elevation myocardial infarction. However, the factors that contribute to failure of achieving door to balloon time ≤ 90 min in an electrocardiogram triage system remain unknown.

Methods

This single-center retrospective observational study collected data from consecutive patients with ST-segment elevation myocardial infarction from April 2016 to March 2021. The primary outcome was the failure to achieve door to balloon time ≤ 90 min. A multivariate logistic regression model was performed to predict factors associated with failure to achieve door to balloon time ≤ 90 min.

Results

In total, 190 eligible patients were included. Of these, the 139 (73.2%) patients with door to balloon time ≤ 90 min were significantly younger compared to those with door to balloon time > 90 min (p = 0.02). However, there was no significant difference in sex and timing of hospital arrival between the door to balloon time ≤ 90 and > 90 min groups. Presence of chest pain and ambulance usage were significantly more frequent in patients with door to balloon time ≤ 90 min (p ≤ 0.01, p = 0.02, respectively). Multivariate analysis showed that absence of chest pain (adjusted odds ratio 4.76; 95% confidence interval, 2.04–11.1; p < 0.01) and non-ambulance usage (adjusted odds ratio 3.53; 95% confidence interval, 1.57–7.94; p < 0.01) are predictive factors of failure to achieve door to balloon time ≤ 90 min.

Conclusion

Patients without chest pain as the chief complaint or non-ambulance usage were significantly associated with the failure to achieve door to balloon time ≤ 90 min.
Transcriptome analysis of the Bactrian camel (Camelus bactrianus) reveals candidate genes affecting milk production traits
Authors: Yao Huaibing , Dou Zhihua , Zhao Zhongkai , Liang Xiaorui , Yue Haitao , Ma Wanpeng , Su Zhanqiang , Wang Yuzhuo , Hao Zelin , Yan Hui , Wu Zhuangyuan , Wang Liang , Chen Gangliang , Yang Jie
Published: November 2023

Background

Milk production traits are complex traits with vital economic importance in the camel industry. However, the genetic mechanisms regulating milk production traits in camels remain poorly understood. Therefore, we aimed to identify candidate genes and metabolic pathways that affect milk production traits in Bactrian camels.

Methods

We classified camels (fourth parity) as low- or high-yield, examined pregnant camels using B-mode ultrasonography, observed the microscopic changes in the mammary gland using hematoxylin and eosin (HE) staining, and used RNA sequencing to identify differentially expressed genes (DEGs) and pathways.

Results

The average standard milk yield over the 300 days during parity was recorded as 470.18 ± 9.75 and 978.34 ± 3.80 kg in low- and high-performance camels, respectively. Nine female Junggar Bactrian camels were subjected to transcriptome sequencing, and 609 and 393 DEGs were identified in the low-yield vs. high-yield (WDL vs. WGH) and pregnancy versus colostrum period (RSQ vs. CRQ) comparison groups, respectively. The DEGs were compared with genes associated with milk production traits in the Animal Quantitative Trait Loci database and in Alashan Bactrian camels, and 65 and 46 overlapping candidate genes were obtained, respectively. Functional enrichment and protein–protein interaction network analyses of the DEGs and candidate genes were conducted. After comparing our results with those of other livestock studies, we identified 16 signaling pathways and 27 core candidate genes associated with maternal parturition, estrogen regulation, initiation of lactation, and milk production traits. The pathways suggest that emerged milk production involves the regulation of multiple complex metabolic and cellular developmental processes in camels. Finally, the RNA sequencing results were validated using quantitative real-time PCR; the 15 selected genes exhibited consistent expression changes.

Conclusions

This study identified DEGs and metabolic pathways affecting maternal parturition and milk production traits. The results provides a theoretical foundation for further research on the molecular mechanism of genes related to milk production traits in camels. Furthermore, these findings will help improve breeding strategies to achieve the desired milk yield in camels.

Graphical Abstract
Transcriptional deciphering of the metabolic pathways associated with the bioactive ingredients of wolfberry species with different quality characteristics
Authors: Liu Xuexia , Zheng Rui , Radani Yasmina , Gao Han , Yue Sijun , Fan Wenqiang , Tang Jianning , Shi Jing , Zhu Jinzhong
Published: November 2023

Background

Wolfberry is rich in carotenoids, flavonoids, vitamins, alkaloids, betaines and other bioactive ingredients. For over 2,000 years, wolfberry has been used in China as a medicinal and edible plant resource. Nevertheless, the content of bioactive ingredients varies by cultivars, resulting in uneven quality across wolfberry cultivars and species. To date, research has revealed little about the underlying molecular mechanism of the metabolism of flavonoids, carotenoids, and other bioactive ingredients in wolfberry.

Results

In this context, the transcriptomes of the Lycium barbarum L. cultivar ‘Ningqi No. 1’ and Lycium chinense Miller were compared during the fruit maturity stage using the Illumina NovaSeq 6000 sequencing platform, and subsequently, the changes of the gene expression profiles in two types of wolfberries were analysed. In total, 256,228,924 clean reads were obtained, and 8817 differentially expressed genes (DEGs) were identified, then assembled by Basic Local Alignment Search Tool (BLAST) similarity searches and annotated using Gene Ontology (GO), Clusters of Orthologous Groups of proteins (KOG), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). By combining these transcriptome data with data from the PubMed database, 36 DEGs related to the metabolism of bioactive ingredients and implicated in the metabolic pathway of carotenoids, flavonoids, terpenoids, alkaloids, vitamins, etc., were identified. In addition, among the 9 differentially expressed transcription factors, LbAPL, LbPHL11 and LbKAN4 have raised concerns. The protein physicochemical properties, structure prediction and phylogenetic analysis indicated that LbAPL and LbPHL11 may be good candidate genes involved in regulating the flavonoid metabolism pathway in wolfberry.

Conclusions

This study provides preliminary evidence for the differences in bioactive ingredient content at the transcription level among different wolfberry species, as well as a research and theoretical basis for the screening, cloning and functional analysis of key genes involved in the metabolism of bioactive ingredients in wolfberry.
Factors associated with mechanical ventilation longer than 24 h after liver transplantation in patients at risk for bleeding
Authors: Caballero Marta , Sabate Antoni , Perez Lourdes , Vidal Julia , Reverter Enric , Gutierrez Rosa , Crespo Gonzalo , Penafiel Judith , Blasi Annabel
Published: November 2023

Background

This risk analysis aimed to explore all modifiable factors associated with prolonged mechanical ventilation (lasting > 24 h) after liver transplantation, based on prospectively collected data from a clinical trial.

Methods

We evaluated 306 candidates. Ninety-three patients were excluded for low risk for transfusion (preoperative haemoglobin > 130 g.l−1), and 31 patients were excluded for anticoagulation therapy, bleeding disorders, familial polyneuropathy, or emergency status. Risk factors were initially identified with a log-binomial regression model. Relative risk was then calculated and adjusted for age, sex, and disease severity (Model for End-Stage Liver Disease [MELD] score).

Results

Early tracheal extubation was performed in 149 patients (84.7%), and 27 patients (15.3%) required prolonged mechanical ventilation. Reoperations were required for 6.04% of the early extubated patients and 44% of patients who underwent prolonged ventilation (p = 0.001). A MELD score > 23 was the main risk factor for prolonged ventilation. Once modifiable risk factors were adjusted for MELD score, sex, and age, three factors were significantly associated with prolonged ventilation: tranexamic acid (p = 0.007) and red blood cell (p = 0.001) infusion and the occurrence of postreperfusion syndrome (p = 0.004). The median (IQR) ICU stay was 3 (2–4) days in the early extubation group vs. 5 (3–10) days in the prolonged ventilation group (p = 0.001). The median hospital stay was also significantly shorter after early extubation, at 14 (10–24) days, vs. 25 (14–55) days in the prolonged ventilation group (p = 0.001). Eight patients in the early-extubation group (5.52%) were readmitted to the ICU, nearly all for reoperations, with no between-group differences in ICU readmissions (prolonged ventilation group, 3.7%). Conclusion.

We conclude that bleeding and postreperfusion syndrome are the main modifiable factors associated with prolonged mechanical ventilation and length of ICU stay, suggesting that trials should explore vasopressor support strategies and other interventions prior to graft reperfusion that might prevent potential fibrinolysis.

Trial Registration.

European Clinical Trials Database (EudraCT 2018–002510-13,) and on ClinicalTrials.gov (NCT01539057).
Management and outcomes of myocardial infarction in people with impaired kidney function in England
Authors: Scott Jemima , Bidulka Patrick , Taylor Dominic M. , Udayaraj Udaya , Caskey Fergus J. , Birnie Kate , Deanfield John , de Belder Mark , Denaxas Spiros , Weston Clive , Adlam David , Nitsch Dorothea
Published: November 2023

Background

Acute myocardial infarction (AMI) causes significant mortality and morbidity in people with impaired kidney function. Previous observational research has demonstrated reduced use of invasive management strategies and inferior outcomes in this population. Studies from the USA have suggested that disparities in care have reduced over time. It is unclear whether these findings extend to Europe and the UK.

Methods

Linked data from four national healthcare datasets were used to investigate management and outcomes of AMI by estimated glomerular filtration rate (eGFR) category in England. Multivariable logistic and Cox regression models compared management strategies and outcomes by eGFR category among people with kidney impairment hospitalised for AMI between 2015–2017.

Results

In a cohort of 5 835 people, we found reduced odds of invasive management in people with eGFR < 60mls/min/1.73m2 compared with people with eGFR ≥ 60 when hospitalised for non-ST segment elevation MI (NSTEMI). The association between eGFR and odds of invasive management for ST-elevation MI (STEMI) varied depending on the availability of percutaneous coronary intervention. A graded association between mortality and eGFR category was demonstrated both in-hospital and after discharge for all people.

Conclusions

In England, patients with reduced eGFR are less likely to receive invasive management compared to those with preserved eGFR. Disparities in care may however be decreasing over time, with the least difference seen in patients with STEMI managed via the primary percutaneous coronary intervention pathway. Reduced eGFR continues to be associated with worse outcomes after AMI.
Cytokine release syndrome was an independent risk factor associated with hypoalbuminemia for patients with relapsed/refractory hematological malignancies after CAR-T cell therapy
Authors: Ding Shuyi , Chen Rongrong , Wang Linqin , Zu Cheng , Zhou Xiaoyu , Zhang Jianli , Zhang Mingming , Jin Aiyun , Wang Tingting , Hu Yongxian
Published: November 2023

Background & aims

This study aims to assess the nutritional status of patients during the different phases of the Chimeric Antigen Receptor (CAR)-T cell therapy and to identify prominent risk factors of hypoalbuminemia in patients after CAR-T treatment. The clinical consequences of malnutrition in cancer patients have been highlighted by growing evidence from previous clinical studies. Given CAR-T cell therapy's treatment intensity and possible side effects, it is important to provide patients with sufficient medical attention and support for their nutritional well-being.

Methods

This study was conducted from May 2021 to December 2021 among patients undergoing CAR-T cell therapy at the Bone Marrow Transplantation Center in The First Affiliated Hospital of Zhejiang University School of Medicine. Logistic regression analysis was performed to investigate the risk factors associated with hypoalbuminemia. Participants were divided into the cytokine release syndrome (CRS) group (n = 60) and the non-CRS group (n = 11) to further analyze the relationship between hypoalbuminemia and CRS.

Results

CRS (OR = 13.618; 95% CI = 1.499–123.709; P = 0.013) and baseline albumin (ALB) (OR = 0.854; 95% CI = 0.754–0.967; P = 0.020) were identified as the independent clinical factors associated with post-CAR-T hypoalbuminemia. According to the nadir of serum albumin, hypoalbuminemia occurred most frequently in patients with severe CRS (78.57%). The nadir of serum albumin (r =  − 0.587, P < 0.001) and serum albumin at discharge (r =  − 0.315, P = 0.01) were negatively correlated for the duration of CRS. Furthermore, patients with hypoalbuminemia deserved longer hospitalization (P = 0.04).

Conclusions

CRS was identified as a significant risk factor associated with post-CAR-T hypoalbuminemia. An obvious decline in serum albumin was observed as the grade and duration of CRS increase. However, further research is still needed to elucidate the mechanisms of CRS-associated hypoalbuminemia.
The combined association of adherence to recommended physical activity and glycemic control with depression: an exploratory study with mediation and moderation models
Authors: Zou Yuchuan , Meng Fanchao , Yan Xiuping
Published: November 2023

Background

Both physical activity and dysglycemia are associated with depression. However, the combined association of adherence to recommended physical activity (RPA) and glycemic control with depression is unknown. Moreover, the extent to which glycemic control mediates the association between physical activity and depression is not established.

Methods

The sample included 31,302 adults from the National Health and Nutrition Examination Survey 2007-08 to 2017-18. Adherence to RPA for aerobic activity was defined according to the WHO 2020 guidelines. HbA1c was classified as < 5.7%, 5.7–6.4%, 6.5–6.9%, and ≥ 7.0%. Depression was evaluated according to the 9-item Patient Health Questionnaire. The odds ratio for depression stratified by adherence to RPA and HbA1c level were estimated by logistic regressions. Mediation analysis was performed to estimate the direct associations (not through glycemic control) and indirect associations (through glycemic control).

Results

A total of 2871 participants were diagnosed with depression. Compared to participants with HbA1c level < 5.7% who adhere to RPA, those with HbA1c level < 5.7%, 5.7-6.4%, 6.5-6.9%, and ≥ 7.0% who did not adhere to RPA had increased odds ratio for depression, especially in women and older adults. Individuals with HbA1c ≥ 7.0% still had an increased odds ratio for depression even though they were physically active. The results of the mediation analysis were insignificant.

Conclusion

There was a combined association of adherence to RPA and glycemic control with depression in women and older adults. We did not find out evidence of glycemic control mediation on the pathway from physical activity to depression.
An early warning precision public health approach for assessing COVID-19 vulnerability in the UK: the Moore-Hill Vulnerability Index (MHVI)
Authors: Moore Harriet , Hill Bartholomew , Emery Jay , Gussy Mark , Siriwardena Aloysius Niroshan , Spaight Robert , Tanser Frank
Published: November 2023

Background

Most COVID-19 vulnerability indices rely on measures that are biased by rates of exposure or are retrospective like mortality rates that offer little opportunity for intervention. The Moore-Hill Vulnerability Index (MHVI) is a precision public health early warning alternative to traditional infection fatality rates that presents avenues for mortality prevention.

Methods

We produced an infection-severity vulnerability index by calculating the proportion of all recorded positive cases that were severe and attended by ambulances at small area scale for the East Midlands of the UK between May 2020 and April 2022. We produced maps identifying regions with high and low vulnerability, investigated the accuracy of the index over shorter and longer time periods, and explored the utility of the MHVI compared to other common proxy measures and indices. Analysis included exploring the correlation between our novel index and the Index of Multiple Deprivation (IMD).

Results

The MHVI captures geospatial dynamics that single metrics alone often overlook, including the compound health challenges associated with disadvantaged and declining coastal towns inhabited by communities with post-industrial health legacies. A moderate negative correlation between MHVI and IMD reflects spatial analysis which suggests that high vulnerability occurs in affluent rural as well as deprived coastal and urban communities. Further, the MHVI estimates of severity rates are comparable to infection fatality rates for COVID-19.

Conclusions

The MHVI identifies regions with known high rates of poor health outcomes prior to the pandemic that case rates or mortality rates alone fail to identify. Pre-hospital early warning measures could be utilised to prevent mortality during a novel pandemic.
Ten-step minimally invasive slalom unilateral laminotomy for bilateral decompression (sULBD) with navigation
Authors: Adelhoefer Siegfried J. , Berger Jessica , Mykolajtchuk Catherine , Gujral Jaskeerat , Boadi Blake I. , Fiani Brian , Härtl Roger
Published: November 2023

Background

Unilateral laminotomy for bilateral decompression (ULBD) is a MIS surgical technique that offers safe and effective decompression of lumbar spinal stenosis (LSS) with a long-term resolution of symptoms. Advantages over conventional open laminectomy include reduced expected blood loss, muscle damage, mechanical instability, and less postoperative pain. The slalom technique combined with navigation is used in multi-segmental LSS to improve the workflow and effectiveness of the procedure.

Methods

We outline ten technical steps to achieve a slalom unilateral laminotomy for bilateral decompression (sULBD) with navigation. In a retrospective case series, we included patients with multi-segmental LSS operated in our institution using the sULBD between 2020 and 2022. The primary outcome was a reduction in pain measured by Visual Analogue Scale (VAS) for back pain and leg pain and Oswestry Disability Index (ODI).

Results

In our case series (N = 7), all patients reported resolution of initial symptoms on an average follow-up of 20.71 ± 9 months. The average operative time and length of hospital stay were 196.14 min and 1.67 days, respectively. On average, VAS (back pain) was 4.71 pre-operatively and 1.50 on long-term follow-up of an average of 19.05 months. VAS (leg pain) decreased from 4.33 to 1.21. ODI was reported as 33% pre-operatively and 12% on long-term follow-up.

Conclusion

The sULBD with navigation is a safe and effective MIS surgical procedure and achieves the resolution of symptoms in patients presenting with multi-segmental LSS. Herein, we demonstrate the ten key steps required to perform the sULBD technique. Compared to the standard sULBD technique, the incorporation of navigation provides anatomic localization without exposure to radiation to staff for a higher safety profile along with a fast and efficient workflow.
Effect of O-arm on reduction quality and functional recovery of acetabular dome impaction fractures: a retrospective clinical study
Authors: Deng Hongli , Cong Yuxuan , Lei Jinlai , Li Dongyang , Ke Chao , Fan Zhiqiang , Wang Hu , Wang Pengfei , Zhuang Yan
Published: November 2023

Background

Acetabular dome impaction fractures (ADIF) are difficult to reduce and have a high failure rate. Consistency between the acetabulum and the femoral head is usually assessed using intraoperative X-ray fluoroscopy to evaluate the quality of fracture reduction. This study examines the effects of intraoperative mobile 2D/3DX imaging system (O-arm) on the reduction quality and functional recovery of ADIF.

Methods

We retrospectively analysed the data of 48 patients with ADIF treated at Honghui Hospital between October 2018 and October 2021.The patients were divided into the X-ray and O-arm groups. The residual step-off and gap displacements in the acetabular dome region were measured, and fracture reduction quality was evaluated. Hip function was evaluated using the modified Merle d’Aubigné and Postel scoring systems.

Results

There were no significant intergroup differences in the preoperative general data (p > 0.05). The mean residual average step displacement in the acetabular dome region was 3.48 ± 2.43 mm and 1.61 ± 1.16 mm (p < 0.05), while the mean gap displacement was 6.72 ± 3.69 mm and 3.83 ± 1.67 mm (p < 0.05) in the X-ray and the O-arm groups, respectively. In the X-ray group, according to the fracture reduction criteria described by Verbeek and Moed et al., one case was excellent, 13 cases were good, 11 cases were poor; 56% were excellent or good. In the O-arm group, seven cases were excellent, 12 cases were good, and four cases were poor; overall in this group, 82.6% were excellent or good (p < 0.05). A total of 46 patients achieved fracture healing at the last follow-up. In the X-ray group, according to the modified Merle d’Aubigné and Postel function score, three cases were excellent,12 cases were good, six cases were middle, three cases were poor; 62.5% were excellent or good, In the O-arm group, 15 cases were excellent, four cases were good, two cases were middle, one case was poor; 86.4% were excellent or good (p < 0.05).

Conclusions

The application of O-arm in ADIF can improve fracture reduction quality and functional recovery.
Associations between apolipoprotein B and bone mineral density: a population-based study
Authors: Zhao Xuefei , Tan Ning , Zhang Ya , Xiao Mengde , Li Lihong , Ning Zhongxing , Liu Mingjiang , Jin Haimin
Published: November 2023

Background

Lipids are critical in bone metabolism, and several studies have highlighted their importance. This study aimed to investigate the relationship between apolipoprotein B (apo B) and bone mineral density (BMD) at different skeletal sites (lumbar spine, femoral neck, and total femur) and to compare the influence of apo B with other traditional lipid markers.

Methods

The study included participants from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2016 who had complete data for apo B and BMD at the three skeletal sites. We used weighted multivariate regression analysis, subgroup analysis, and interaction tests to examine associations. Restricted cubic spline (RCS) was used to examine the non-linear relationship.

Results

A total of 4,258 adults were included in the study. Multivariate linear regression analysis showed that the relationship between apo B and BMD varied by skeletal site: a negative association was found with lumbar spine BMD [β = -0.054, 95%CI: (-0.073, -0.035)]. In contrast, a positive association was found with femoral neck BMD [β = 0.031, 95%CI: (0.011, 0.051)] and no significant association between apo B and total femur BMD.

Conclusions

Our findings suggest that apo B is associated with BMD in a site-specific manner.
Development and validation of a tool to assess researchers’ knowledge of human subjects’ rights and their attitudes toward research ethics education in Saudi Arabia
Authors: Al-Madaney May M. , Fässler Margrit
Published: November 2023

Background

Researchers must adhere to ethical and scientific standards in their research involving human subjects; therefore, their knowledge of human subjects’ rights is essential. A tool to measure the extent of this knowledge is necessary to ensure that studies with participants are conducted ethically and to enhance research integrity. Currently, no validated instrument is available for such an assessment. Therefore, the primary purpose of this study is to develop a reliable and valid instrument to assess researchers’ knowledge of human subjects’ rights in clinical settings, as well as a reliable and valid measure of their attitudes toward clinical research ethics education in Saudi Arabia.

Methods

The current study involves the development of a questionnaire about the rights of human subjects in research and the researchers’ attitudes toward research ethics education. The content was developed based on an extensive review of research ethics guidelines. A panel of experts tested the questionnaire for face validity (n = 5) and content validity (n = 8). The reliability of the questionnaire was established by a split-half reliability coefficient and item analysis among a sample (n = 301) of clinical researchers.

Results

Face validity demonstrated that the questionnaire was quick to complete and easy to answer. The global content validity indices (S-CVIs) were greater than 0.78 for all questionnaire sections; the split-half reliability coefficient was 0.755 for knowledge items; Cronbach’s alpha was 0.77 for researchers’ attitudes, showing good internal consistency. The difficulty index ranged from 12.0% to 98.7% for all knowledge items. Most questions were at an acceptable level of reliability and discrimination criteria. The final version of the questionnaire contained 89 items, distributed as 15 questions on demographic and professional characteristics, 64 questions items on knowledge, and 10 items on attitudes.

Conclusions

The questionnaire is a valid and reliable tool to assess biomedical researchers’ knowledge of human subjects’ rights and their attitudes toward research ethics education. This instrument could help address the gap in researchers’ knowledge of the rights and facilitate the development of educational intervention programs to set appropriate learning objectives.
A lowered threshold to partnerships: a mixed methods process evaluation of participants’ experiences of a person-centred eHealth intervention
Authors: Cederberg Matilda , Barenfeld Emmelie , Ali Lilas , Ekman Inger , Goulding Anneli , Fors Andreas
Published: November 2023

Background

In order to understand pathways of complex interventions, the Medical Research Council has suggested that process evaluations should be conducted alongside randomised controlled trials (RCTs). This paper presents a mixed methods process evaluation of a complex, person-centred eHealth intervention for persons on sick leave with common mental disorders.

Aim

The aim of the study was to explore participants’ experiences of a person-centred eHealth intervention and illuminate meaningful activities and processes.

Methods

Participants were recruited from the intervention arm of an RCT (n = 102). Questionnaires on perceived meaningfulness of the overall intervention and intervention activities were sent to participants on two occasions, after 3 and 6 months, and semi-structured interviews were conducted with a purposeful sample of 15 participants in the intervention group. Questionnaire data were analysed using descriptive statistics, and interview data were analysed using qualitative content analysis. The quantitative and qualitative data strands were integrated at interpretation.

Results

At both follow-ups, a majority of participants reported that the intervention was fully or partly meaningful and that the most meaningful activity was the phone calls with health care professionals working in the intervention. In the qualitative analysis, three categories describing participants’ experiences of the intervention were formed: Acknowledgment in a disconcerting situation, Finding ways forward and Unmet expectations. A synthesis of quantitative and qualitative findings resulted in the overarching theme of meaningfulness as constituted by a lowered threshold to partnerships: support within reach, when needed.

Conclusion

Experiences of meaningfulness of the intervention were constituted by a lowered threshold to forming care partnerships, in which support was within reach, when needed. If the content of the intervention was not in accordance with individuals’ needs or expectations, access alone did not suffice to constitute meaningfulness.

Trial registration

ClinicalTrials.gov; NCT03404583; 19/01/2018.
Evaluation of risk factors for treatment failure in canine patients undergoing photoactivated chromophore for keratitis – corneal cross-linking (PACK-CXL): a retrospective study using additive bayesian network analysis
Authors: Kowalska M. E. , Shukla A. K. , Arteaga K. , Crasta M. , Dixon C. , Famose F. , Hartnack S. , Pot S. A.
Published: November 2023

Background

Infectious keratitis is a common ophthalmic condition in canine patients. Sequelae can include keratomalacia and corneal perforation, a vision threatening outcome. Photoactivated chromophore for keratitis – corneal cross-linking (PACK-CXL) is a non-surgical, adjunctive treatment method for infectious keratitis. The goal of this retrospective, multicenter study was to determine risk factors for treatment failure following PACK-CXL in canine patients suffering from suspected infectious keratitis. Medical records from four veterinary ophthalmology services were reviewed, and information related to patient demographics, ophthalmic findings, the PACK-CXL protocol used, and epithelialization time was collected and analyzed. Due to the potential for intervariable relationships, an additive Bayesian network (ABN) analysis was performed to evaluate these complex relationships.

Results

Records for 671 eyes (668 dogs) were included in the analysis. Based on the ABN, in the population included here, patients who underwent an accelerated PACK-CXL protocol were less likely to experience treatment failure versus patients treated with a slow protocol. Mutual dependencies between exposure variables were identified by ABN, which would have been overlooked using classical regression. Corneal re-epithelialization time was shortened following PACK-CXL combined with topical medical therapy compared to PACK-CXL alone.

Conclusions

No risk factors associated with treatment failure were identified in the population included in the present study. Canine patients may benefit from the use of accelerated PACK-CXL protocols, especially when combined with topical antibiotics and anti-collagenolytic therapy. The reasons for this apparent positive impact on treatment outcome remain unclear.
Causal association of epigenetic aging and osteoporosis: a bidirectional Mendelian randomization study
Authors: Liang Xinyu , Shi Wei , Zhang Xinglong , Pang Ran , Zhang Kai , Xu Qian , Xu Chunlei , Wan Xin , Cui Wenhao , Li Dong , Jiang Zhaohui , Liu Zhengxuan , Li Hui , Zhang Huafeng , Li Zhijun
Published: November 2023

Background

The relationship between aging and osteoporosis is well established. However, the relationship between the body's physiological age, i.e. epigenetic age, and osteoporosis is not known. Our goal is to analyze the bidirectional causal relationship between epigenetic clocks and osteoporosis using a bidirectional Mendelian randomization study.

Methods

We used SNPs closely associated with GrimAge, Hannum, PhenoAge, and HorvathAge in epigenetic age and SNPs closely associated with femoral neck bone mineral density, lumbar spine bone mineral density, and forearm bone mineral density as instrumental variables, respectively, using the inverse variance weighting method and several other MR methods to assess the bidirectional causal relationship between epigenetic age and osteoporosis.

Result

There was no evidence of a clear causal relationship of epigenetic age (GrimAge, Hannum, PhenoAge, and HorvathAge) on femoral neck bone mineral density, lumbar spine bone mineral density, and forearm bone mineral density. In reverse Mendelian randomization analysis showed a significant causal effect of lumbar spine bone mineral density on GrimAge: odds ratio (OR) = 0.692, 95% confidence interval (CI) = (0.538–0.890), p = 0.004. The results suggest that a decrease in lumbar spine bone mineral density promotes an acceleration of GrimAge.

Conclusion

There was no significant bidirectional causal relationship between epigenetic age and osteoporosis A decrease in lumbar spine bone density may lead to an acceleration of the epigenetic clock "GrimAge". Our study provides partial evidence for a bidirectional causal effect between epigenetic age and Osteoporosis.
High BMI and the risk for incident type 1 Diabetes Mellitus: a systematic review and meta-analysis of aggregated cohort studies
Authors: Nitecki Maya , Gerstein Hertzel C. , Balmakov Yulia , Tsur Eyal , Babushkin Vladislav , Michaeli Tomer , Afek Arnon , Pinhas-Hamiel Orit , Cukierman-Yaffe Tali , Twig Gilad
Published: November 2023

Background

There is uncertainty regarding the role of obesity in type 1 diabetes development. The aim of this systematic review and meta-analysis was to collect and synthesize evidence regarding BMI and the risk of developing type 1 diabetes.

Methods

A systematic review and meta-analysis were conducted to assess the association between BMI and incident type 1 diabetes. Databases were searched up to June 2022. Cohort studies were included reporting the association between overweight and/or obesity, as measured by BMI after age 2 years, with incident type 1 diabetes. Independent reviewers extracted data and assessed study quality. Risk estimates were pooled using a random-effects model.

Results

Ten cohort studies met the inclusion criteria. The seven studies that classified BMI into categories were of high quality and involved 1,690,660 individuals and 1979 incident type 1 diabetes cases. The pooled risk ratio (RR) for type 1 diabetes was 1.35 (95% CI 0.93–1.97) among people with overweight (3 studies); 2.17 (95% CI 1.75–2.69) among people with obesity (5 studies); and 1·87 (95% CI 1.52–2.29) among people with overweight/obesity (two studies merged the categories). These point estimates persisted in sensitivity analyses that addressed the duration of follow-up, variability in baseline risk for incident type 1 diabetes, and potential misclassifications related to exposure or outcome definitions. People with overweight/obesity had a 2.55 (95% CI 1.11–5.86) greater risk for incident type 1 diabetes with positive islet autoantibodies.

Conclusion

This systematic review and meta-analysis of high-quality observational cohort studies indicated an association between high BMI and the risk of type 1 diabetes, in a graded manner.
Cardioprotective function of sclerostin by reducing calcium deposition, proliferation, and apoptosis in human vascular smooth muscle cells
Authors: González-Salvatierra Sheila , García-Fontana Cristina , Lacal Jesus , Andújar-Vera Francisco , Martínez-Heredia Luis , Sanabria-de la Torre Raquel , Ferrer-Millán María , Moratalla-Aranda Enrique , Muñoz-Torres Manuel , García-Fontana Beatriz
Published: November 2023

Background

Sclerostin is an inhibitor of the Wnt/b-catenin pathway, which regulates bone formation, and can be expressed in vascular smooth muscle cells (VSMCs). Type 2 diabetes (T2D) is associated with an increased risk of cardiovascular disease (CVD) and increased serum and tissue expression of sclerostin. However, whether the role of sclerostin is detrimental or protective in the development of CVD is unknown. Therefore, our aims are to determine the level of sclerostin in T2D patients with/without CVD and in controls, both at serum and vascular tissue, and to analyze the role of sclerostin in VSMCs under calcified environments.

Methods

Cross-sectional study including 121 controls and 139 T2D patients with/without CVD (48/91). Sclerostin levels in serum were determined by ELISA, and sclerostin expression was analyzed by RT-qPCR and immunohistochemistry in calcified and non-calcified artery of lower limb from T2D patients (n = 7) and controls (n = 3). In vitro experiments were performed in VSMCs (mock and sclerostin overexpression) under calcifying conditions analyzing the sclerostin function by determination of calcium and phosphate concentrations, and quantification of calcium deposits by Alizarin Red. Proliferation and apoptosis were analyzed by MTT assay and flow cytometry, respectively. The regulation of the expression of genes involved in bone metabolism was determined by RT-qPCR.

Results

A significant increase in serum sclerostin levels in T2D patients with CVD compared to T2D patients without CVD and controls (p < 0.001) was observed. Moreover, higher circulating sclerostin levels were independently associated with CVD in T2D patients. Increased sclerostin expression was observed in calcified arteries of T2D patients compared to non-calcified arteries of controls (p = 0.003). In vitro experiments using VSMCs under calcified conditions, revealed that sclerostin overexpression reduced intracellular calcium (p = 0.001), calcium deposits (p < 0.001), cell proliferation (p < 0.001) and promoted cell survival (p = 0.015). Furthermore, sclerostin overexpression exhibited up-regulation of ALPL (p = 0.009), RUNX2 (p = 0.001) and COX2 (p = 0.003) and down-regulation of inflammatory genes, such as, IL1β (p = 0.005), IL6 (p = 0.001) and IL8 (p = 0.003).

Conclusions

Sclerostin could play a protective role in the development of atherosclerosis in T2D patients by reducing calcium deposits, decreasing proliferation and inflammation, and promoting cell survival in VSMCs under calcifying conditions. Therefore, considering the bone-vascular axis, treatment with anti-sclerostin for bone disease should be used with caution.

Graphical Abstract
Exploring the role of the disulfidptosis-related gene SLC7A11 in adrenocortical carcinoma: implications for prognosis, immune infiltration, and therapeutic strategies
Authors: Liu Tonghu , Ren Yilin , Wang Qixin , Wang Yu , Li Zhiyuan , Sun Weibo , Fan Dandan , Luan Yongkun , Gao Yukui , Yan Zechen
Published: November 2023

Background

Disulfidptosis and the disulfidptosis-related gene SLC7A11 have recently attracted significant attention for their role in tumorigenesis and tumour management. However, its association with adrenocortical carcinoma (ACC) is rarely discussed.

Methods

Differential analysis, Cox regression analysis, and survival analysis were used to screen for the hub gene SLC7A11 in the TCGA and GTEx databases and disulfidptosis-related gene sets. Then, we performed an association analysis between SLC7A11 and clinically relevant factors in ACC patients. Univariate and multivariate Cox regression analyses were performed to evaluate the prognostic value of SLC7A11 and clinically relevant factors. Weighted gene coexpression analysis was used to find genes associated with SLC7A11. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and the LinkedOmics database were used to analyse the functions of SLC7A11-associated genes. The CIBERSORT and Xcell algorithms were used to analyse the relationship between SLC7A11 and immune cell infiltration in ACC. The TISIDB database was applied to search for the correlation between SLC7A11 expression and immune chemokines. In addition, we performed a correlation analysis for SLC7A11 expression and tumour mutational burden and immune checkpoint-related genes and assessed drug sensitivity based on SLC7A11 expression. Immunohistochemistry and RT‒qPCR were used to validate the upregulation of SLC7A11 in the ACC.

Results

SLC7A11 is highly expressed in multiple urological tumours, including ACC. SLC7A11 expression is strongly associated with clinically relevant factors (M-stage and MYL6 expression) in ACC. SLC7A11 and the constructed nomogram can accurately predict ACC patient outcomes. The functions of SLC7A11 and its closely related genes are tightly associated with the occurrence of disulfidptosis in ACC. SLC7A11 expression was tightly associated with various immune cell infiltration disorders in the ACC tumour microenvironment (TME). It was positively correlated with the expression of immune chemokines (CXCL8, CXCL3, and CCL20) and negatively correlated with the expression of immune chemokines (CXCL17 and CCL14). SLC7A11 expression was positively associated with the expression of immune checkpoint genes (NRP1, TNFSF4, TNFRSF9, and CD276) and tumour mutation burden. The expression level of SLC7A11 in ACC patients is closely associated withcthe drug sensitivity.

Conclusion

In ACC, high expression of SLC7A11 is associated with migration, invasion, drug sensitivity, immune infiltration disorders, and poor prognosis, and its induction of disulfidptosis is a promising target for the treatment of ACC.
Human papillomavirus infections among women with cervical lesions and cervical cancer in Yueyang, China: a cross-sectional study of 3674 women from 2019 to 2022
Authors: Zeng Min , Zhang Xiaoyun , He LiLi , Liu Xin , Liu Huawen , Deng Rui , Qiu Bo , Liu Fang , Xiao Hang , Li Quanlv , Li Wen , Liu Chongmei , Ge Yangqing
Published: November 2023

Purpose

To investigate the distribution of the incidence and genotypes of human papillomavirus (HPV) among women with cervical cancer (CC) and precancerous cervical lesions in Yueyang City, China, to develop prevention and control strategies for CC.

Methods

A total of 3674 patients with cervical lesions and cervical cancer who attended 7 hospitals in Yueyang City between September 2019 and September 2022 were included. They included 1910 cervical intraepithelial neoplasia (CIN) I, 718 CIN II, 576 CIN II and 470 CC, respectively. The HPV genotyping of the above patients was detected by Real time-PCR in the laboratory department of each hospital.

Results

The total HPV prevalence was 74.69% (95% CI 73.28–76.09%) in 3674 patients. The incidence of high- and low-risk HPV was 73.46% and 7.21%, respectively. The prevalence of HPV in CIN I, CIN II, CIN III, and invasive CC (ICC) groups was 66.65% (1273/1910, 95% CI 64.53–68.77%), 80.78% (580/718, 95% CI 77.89–83.67%), 83.88% (483/576, 95% CI 80.84–86.87%), and 86.81% (408/470, 95% CI 83.74–89.88%), respectively. The top three HPV subtypes in ICC are HPV16, HPV52, and HPV58. The prevalence of HPV 16 increased with increasing disease severity, with this genotype being present in 12.57%, 20.89%, 36.98%, and 50.85% of CIN I, CIN II, CIN III, and ICC cases, respectively (p < 0.001). Single HPV infection was predominant in cervical lesions, with a prevalence of 48.50% (95% CI 46.89–50.12%). The HPV prevalence varied by age, being highest among women with ICC, CIN I, CIN II and CIN III aged ≥ 60 years, 50–59 years, 40–49 years, and 40–49 years, respectively.

Conclusion

The prevalence of HPV in patients with cervical lesions in Yueyang City was very high, with HPV 16, 52, 58, 53, and 51 being the five most common HPV genotypes in patients with cervical lesions.