bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipidomic and transcriptomic profiles of glycerophospholipid metabolism during Hemerocallis citrina Baroni flowering
Authors: Guo Aihua , Yang Yang , Wu Jiang , Qin Nannan , Hou Feifan , Gao Yang , Li Ke , Xing Guoming , Li Sen
Published: January 2023

Background

Hemerocallis citrina Baroni (daylily) is a horticultural ornamental plant and vegetable with various applications as a raw material in traditional Chinese medicine and as a flavouring agent. Daylily contains many functional substances and is rich in lecithin, which is mostly composed of glycerophospholipids. To study the comprehensive dynamic changes in glycerophospholipid during daylily flowering and the underlying signalling mechanisms, we performed comprehensive, time-resolved lipidomic and transcriptomic analyses of ‘Datong Huanghua 6’ daylily.

Results

Labelling with PKH67 fluorescent antibodies clearly and effectively helped visualise lipid changes in daylily, while relative conductivity and malonaldehyde content detection revealed that the early stages of flowering were controllable processes; however, differences became non-significant after 18 h, indicating cellular damage. In addition, phospholipase D (PLD) and lipoxygenase (LOX) activities increased throughout the flowering process, suggesting that lipid hydrolysis and oxidation had intensified. Lipidomics identified 558 lipids that changed during flowering, with the most different lipids found 12 h before and 12 h after flowering. Transcriptome analysis identified 13 key functional genes and enzymes in the glycerophospholipid metabolic pathway. The two-way orthogonal partial least squares analysis showed that diacylglycerol diphosphate phosphatase correlated strongly and positively with phosphatidic acid (PA)(22:0/18:2), PA(34:2), PA(34:4), and diacylglycerol(18:2/21:0) but negatively with phospholipase C. In addition, ethanolamine phosphotransferase gene and phospholipid-N-methyltransferase gene correlated positively with phosphatidylethanolamine (PE)(16:0/18:2), PE(16:0/18:3), PE(33:2), and lysophosphatidylcholine (16:0) but negatively with PE(34:1).

Conclusions

Overall, this study elucidated changes in the glycerophospholipid metabolism pathway during the daylily flowering process, as well as characteristic genes, thus providing a basis for future studies of glycerophospholipids and signal transduction in daylilies.
Transcription elongation factor AtSPT4-2 positively modulates salt tolerance in Arabidopsis thaliana
Authors: Liaqat Ayesha , Alfatih Alamin , Jan Sami Ullah , Sun Liangqi , Zhao Pingxia , Xiang Chengbin
Published: January 2023

Background

Salt stress significantly influences plant growth and reduces crop yield. It is highly anticipated to develop salt-tolerant crops with salt tolerance genes and transgenic technology. Hence, it is critical to identify salt tolerance genes that can be used to improve crop salt tolerance.

Results

We report that the transcription elongation factor suppressor of Ty 4-2 (SPT4-2) is a positive modulator of salt tolerance in Arabidopsis thaliana. AtSPT4-2 expression is induced by salt stress. Knockout mutants of AtSPT4-2 display a salt-sensitive phenotype, whereas AtSPT4-2 overexpression lines exhibit enhanced salt tolerance. Comparative transcriptomic analyses revealed that AtSPT4-2 may orchestrate the expression of genes associated with salt tolerance, including stress-responsive markers, protein kinases and phosphatases, salt-responsive transcription factors and those maintaining ion homeostasis, suggesting that AtSPT4-2 improves salt tolerance mainly by maintaining ion homeostasis and enhancing stress tolerance.

Conclusions

AtSPT4-2 positively modulates salt tolerance by maintaining ion homeostasis and regulating stress-responsive genes and serves as a candidate for the improvement of crop salt tolerance.
Incidence of postoperative hypothermia and shivering and risk factors in patients undergoing malignant tumor surgery: a retrospective study
Authors: Xu Rongrong , Hu Xinyi , Sun Zhirong , Zhu Xuqin , Tang Yonghong
Published: January 2023

Background

Perioperative hypothermia and shivering are common and can cause adverse outcomes. The aim of this study was to investigate the incidence of postoperative hypothermia and shivering and their risk factors in patients undergoing malignant tumor surgery.

Methods

This retrospective study collected data from patients with American Society of Anesthesiologists physical status (ASA) I or II who underwent scheduled surgery from November 2020 to March 2021 at Fudan University Shanghai Cancer Center. Each patient’s core body temperature was measured at three time points: time point 1 (arrival at the postanesthesia care unit (PACU)), time point 2 (after 30-min care in the PACU), and time point 3 (at discharge from the PACU). At time point 1, if the patient’s body temperature was below 36 ℃, we provided an active forced-air warmer. At time point 2, if it was still below 36 ℃, the forced-air warmer was still applied until the patient was discharged from the PACU. If it reached 36 ℃, the forced-air warmer would be switched off. Univariate and multivariate logistic regression combined with stepwise methods and linear regression were used to explore risk factors for postoperative hypothermia and shivering.

Results

The numbers (percentage) of 202 patients who developed postoperative hypothermia at the different time points were 52 (25.7%), 37 (18.3%) and 28 (13.9%). Eight patients (4.0%) experienced shivering. Multivariate logistic regression showed that high weight (OR = 0.923, 95% CI: 0.884 to 0.964, P = 0.0003) and low estimated blood loss (OR = 0.252, 95% CI: 0.115 to 0.550, P = 0.0005) were protective factors against hypothermia, while long surgical duration (OR = 3.339, 95% CI: 1.675 to 6.655, P = 0.0006) was an independent risk factor for hypothermia at time point 1. There was no risk factor associated with the occurrence of shivering (P > 0.05). There was a significant difference between the hypothermia and normothermia groups in the median length of stay in the PACU (59.0 vs. 49.0 min, P = 0.0123).

Conclusions

Postoperative hypothermia occurred frequently. Weight, estimated blood loss and surgical duration were significantly associated with hypothermia on arrival at the PACU.
Incidence management system of the healthcare institutions for disaster management in Sri Lanka
Authors: Rajapaksha Nayani Umesha , Abeysena Chrishantha , Balasuriya Aindralal , Wijesinghe Millawage Supun Dilara , Manilgama Suranga , Alemu Yibeltal Assefa
Published: January 2023

Background

Incident management systems and disaster planning processes facilitate maximal use of available resources. Evaluation of the Incident Command System (ICS) is one of the top five key areas of research priority in the field of surge. The study was aimed at assessing the disaster preparedness and ICS of the public healthcare institutions for the disaster management in a disaster-prone district of Sri Lanka.

Methods

A descriptive cross-sectional study was conducted among all public sector healthcare institutions (n = 74), including curative-healthcare institutions (n = 46) which have inward-care facilities for patient care and preventive healthcare institutions (n = 28) in Kurunegala district, Sri Lanka from May–September 2019 using a validated interviewer administered questionnaire which was based on ‘CO-S-TR Model’ for ICS assessment including ‘Clear need for increased capacity (≤25%), Basic level (26 – 50%), Moderate level (51 – 75%) and High level (>75%)’.

Results

Focal points for disaster management were nominated by the majority of the curative sector (n = 33; 76.7%) and preventive sector (n = 19; 73.1%) healthcare institutions. A written disaster preparedness and response plans were available in 72% (n= 31) curative sector and 76% (n= 19) preventive sector institutions. The higher proportion of the curative sector institutions had moderate level capacity in the area of providing treatment, and basic level capacities were in the areas of ‘staff mobilization, coordination of activities, supplying of special needs, triage of cases and transportation’. There is a clear need for improvement in the areas of communication commanding, management of controlling the incidence and tracking of the cases in the curative sector. The majority of the preventive sector institutions had moderate level capacity in commanding, control, coordination and tracking of cases. The basic level capacity in the areas of staff mobilization, stuff management and triage of cases. There is a clear need for improvement in the areas of communication in preventive sector. Of the public sector healthcare institutions, the higher proportion of the preventive sector (n = 20; 76.9%) and curative sector (n = 29; 67.4%) had basic level overall surge capacity of ICS for disaster management.

Conclusion

Coordination, communication, commanding, management of controlling the incidence and tracking of cases following outbreaks need to be improved and capacity development programmes could implement to develop the preparedness for future disasters.
The use and impact of digital COVID-19 tracking in adult social care: a prospective cohort study of care homes in Greater Manchester
Authors: Ullah Akbar , Whittaker William , Bradley Fay , Nelson Pauline A. , Dowding Dawn , Morciano Marcello , Cullum Nicky
Published: January 2023

Background

To support proactive care during the coronavirus pandemic, a digital COVID-19 symptom tracker was deployed in Greater Manchester (UK) care homes. This study aimed to understand what factors were associated with the post-uptake use of the tracker and whether the tracker had any effects in controlling the spread of COVID-19.

Methods

Daily data on COVID-19, tracker uptake and use, and other key indicators such as staffing levels, the number of staff self-isolating, availability of personal protective equipment, bed occupancy levels, and any problems in accepting new residents were analysed for 547 care homes across Greater Manchester for the period April 2020 to April 2021. Differences in tracker use across local authorities, types of care homes, and over time were assessed using correlated effects logistic regressions. Differences in numbers of COVID-19 cases in homes adopting versus not adopting the tracker were compared via event design difference-in-difference estimations.

Results

Homes adopting the tracker used it on 44% of days post-adoption. Use decreased by 88% after one year of uptake (odds ratio 0.12; 95% confidence interval 0.06–0.28). Use was highest in the locality initiating the project (odds ratio 31.73; 95% CI 3.76–268.05). Care homes owned by a chain had lower use (odds ratio 0.30; 95% CI 0.14–0.63 versus single ownership care homes), and use was not associated with COVID-19 or staffing levels. Tracker uptake had no impact on controlling COVID-19 spread. Staff self-isolating and local area COVID-19 cases were positively associated with lagged COVID-19 spread in care homes (relative risks 1.29; 1.2–1.4 and 1.05; 1.0–1.1, respectively).

Conclusions

The use of the COVID-19 symptom tracker in care homes was not maintained except in Locality 1 and did not appear to reduce the COVID-19 spread. COVID-19 cases in care homes were mainly driven by care home local-area COVID-19 cases and infections among the staff members. Digital deterioration trackers should be co-produced with care home staff, and local authorities should provide long-term support in their adoption and use.
Effect of an electronic reminder of follow-up screening after pregnancy complicated by gestational diabetes mellitus: a randomized controlled trial
Authors: Nielsen Jane Hyldgaard , Fonager Kirsten , Kristensen Jette Kolding , Overgaard Charlotte
Published: January 2023

Aim

To determine the effectiveness of despatching an electronic reminder of participation in screening for gestational diabetes. The reminder was sent to the women 1–8 years after delivery.

Methods

A registry-based, randomized controlled trial in the North Denmark Region among women with gestational diabetes. Randomization was made, which included seven groups stratified by the child’s birth year (2012–2018). The intervention group received standard care supplemented by an electronic reminder through a secure nationwide email system (n = 731), while the control group received only standard care (n = 732). The primary outcome was based on blood testing for diabetes (OGTT, HbA1c or fasting P-glucose).

Results

A total of 471 (32.1%) women participated in screening. The primary outcome was experienced by 257 women (35.1%) in the intervention group and 214 women (29.2%) in the control group. The effect of the reminder seemed to increase with recipient’s age, non-western origin, urban dwelling, and multiparity. Of those who participated in follow-up screening, 56 (3.8%) were diagnosed with type 2 diabetes.

Conclusion

Electronic reminders, based on the principles of informed choice and patient-centred care, to women have been shown to support life-long participation in follow-up screening. Attempts to further stimulation of coverage could however be considered.

Trail registration

ISRCTN registry (22/04/2022, ISRCTN23558707).
The moderating effect of parental skills for antibiotic identification on the link between parental skills for antibiotic use and inappropriate antibiotic use for children in China
Authors: Yan Bo , He Zhenke , Dong Shixin , Akezhuoli Hailati , Xu Xin , Wang Xiaomin , Zhou Xudong
Published: January 2023

Background

Inappropriate antibiotic consumption promotes antibiotic resistance. However, findings on the association between antibiotic-related knowledge and behaviors are inconsistent and contradictory, resulting in unjustified guidance of interventions. The mechanisms between the different kinds of antibiotic-related skills contained in knowledge modules in some previous studies are indistinct and rarely studied.

Methods

A cross-sectional survey was conducted between June 2017 and April 2018 in three Chinese provinces, investigating 9526 parents with children aged 0–13 years old. Data from 1944 parents who self-medicated their children and 2478 respondents whose children sought care were analyzed.

Results

Skills for antibiotic identification were found to be a moderator for the association between skills for antibiotic use and two inappropriate behaviors. Compared with parents with low levels of both skills for antibiotic identification and use, those mastering both skills at either medium (OR = 0.48, 95% CI [0.26–0.88]) or high (OR = 0.15, 95% CI [0.07–0.34]) level were less likely to self-medicate their children with antibiotics. Parents with a medium level of skills for antibiotic identification and high level of skills for antibiotic use (OR = 0.18, 95% CI [0.08–0.44]) and those with a high level of both skills (OR = 0.15, 95% CI [0.05–0.47]) were less likely to ask doctors for antibiotics when seeking care.

Conclusion

Parents’ high level of skills for antibiotic identification is revealed to promote inappropriate antibiotic use when parents master a low level of skills for antibiotic use. Conversely, based on excellent skills for antibiotic use, better skill for antibiotic identification is associated with a greater reduction in inappropriate behaviors. We recommend future health education to strengthen skills for antibiotic identification along with guidance on antibiotic use.
FAM83B promotes the invasion of primary lung adenocarcinoma via PI3K/AKT/NF-κB pathway
Authors: Zhang Jing , Wang Jiajia , Yue Ke , Li Panpan , Shen Wenping , Qiao Xiaowen , Wang Yan , Wu Xiaojuan
Published: January 2023

Objects

The family with sequence similarity 83B (FAM83B) is one of the markers for poor prognosis in several carcinomas, but the expression and the mechanism resulted in malignant phenotype in lung adenocarcinoma (LUAD) remain to be elucidated.

Methods

 Data of RNA-seq in LUAD were downloaded from the cancer genome atlas (TCGA) database for differential expression and survival analysis, and immunohistochemistry was employed to analyze the protein expression of FAM83B in 126 cases of primary LUAD. The LUAD cell lines were collected for the detection of the effects on migration and invasion. Then, western blot was performed to measure the expression of tissue inhibitor of metalloproteinase (TIMP)-1 and activation of PI3K/AKT/NF-κB pathway.

Results

FAM83B was overexpressed in multiple types of carcinomas; The differential expression analysis revealed that the level of FAM83B was higher in LUAD than that in para-carcinoma; The patients with overexpression of FAM83B were with shorter overall survival (OS), disease specific survival (DSS) and progress free interval (PFI); Enrichment analysis suggested it was related to the focal adhesion of LUAD. Immunohistochemistry analysis demonstrated that higher FAM83B expression was positively related to lymph node metastasis in primary. Scratch assay and Borden chamber assay showed that the overexpression of FAM83B promoted migration and invasion activity in vitro. Furthermore, high level of FAM83B accelerated the tumorigenesis in vivo. Western blot showed that TIMP-1 was upregulated in H1299/FAM83B OE cells accompanying by the activation of PI3K/AKT/NF-κB pathway.

Conclusions

FAM83B was a marker for poor prognosis of LUAD and it might promote the expression of TIMP-1 by activating PI3K/AKT/NF-κB pathway and then affect the ECM balance, which resulted in the migration and invasion of LUAD.
Alteration in coracohumeral ligament and distance in people with symptoms of subcoracoid impingement
Authors: Ting Deng Siang , Yang Jing-lan , Lin Kwan-Hwa , Wang Tyng-Guey , Lin Jiu-Jenq
Published: January 2023

Background

Differentiation between subacromial impingement versus subcoracoid impingement are important for the treatment target. We evaluated the correlations between coracohumeral ligament (CHL) thickness and distance (CHD) and characterized the CHL and subscapularis (SSC) in subcoracoid impingement subjects.

Methods

An observational, cross-sectional study was carried out. Twenty subcoracoid impingement subjects and age/gender matched controls were assessed in 4 different shoulder positions by ultrasonography.

Results

Moderate correlations between CHL thickness with CHD (r = 0.455 in neutral rotation, p = 0.044; r = 0.483 in interior rotation, p = 0.031) were found in subacromial subjects. Subcoracoid impingement subjects had greater CHL thickness (difference = 0.3 mm, effect size = 0.85, p = 0.006), SSC tendon thickness (difference = 0.7 mm, effect size = 0.92, p = 0.01) and SSC/CHD occupation ratio (difference = 8%, effect size = 0.95, p = 0.005) compared with the control.

Conclusions

Coracohumeral distance is related to ligament thickness, especially in subacromial impingement subjects. Increased coracohumeral ligament and subscapularis thickness as well as decreased subscapularis/coracohumeral distance occupation ratio are characterized in subcoracoid impingement subjects. These quantitative measurements can be useful in identifying patients at risk of subcoracoid impingement from subacromial impingement.
The burden of low back pain and its association with socio-demographic variables in the Middle East and North Africa region, 1990–2019
Authors: Safiri Saeid , Nejadghaderi Seyed Aria , Noori Maryam , Sullman Mark J. M. , Collins Gary S. , Kaufman Jay S. , Hill Catherine L. , Kolahi Ali-Asghar
Published: January 2023

Background

Low back pain (LBP) is the most common musculoskeletal disorder globally. Providing region- and national-specific information on the burden of low back pain is critical for local healthcare policy makers. The present study aimed to report, compare, and contextualize the prevalence, incidence and years lived with disability (YLDs) of low back pain in the Middle East and North Africa (MENA) region by age, sex and sociodemographic index (SDI), from 1990 to 2019.

Methods

Publicly available data were obtained from the Global Burden of Disease (GBD) study 2019. The burden of LBP was reported for the 21 countries located in the MENA region, from 1990 to 2019. All estimates were reported as counts and age-standardised rates per 100,000 population, together with their corresponding 95% uncertainty intervals (UIs).

Results

In 2019, the age-standardised point prevalence and incidence rate per 100,000 in MENA were 7668.2 (95% UI 6798.0 to 8363.3) and 3215.9 (95%CI 2838.8 to 3638.3), which were 5.8% (4.3 to 7.4) and 4.4% (3.4 to 5.5) lower than in 1990, respectively. Furthermore, the regional age-standardised YLD rate in 2019 was 862.0 (605.5 to 1153.3) per 100,000, which was 6.0% (4.2 to 7.7) lower than in 1990. In 2019, Turkey [953.6 (671.3 to 1283.5)] and Lebanon [727.2 (511.5 to 966.0)] had the highest and lowest age-standardised YLD rates, respectively. There was no country in the MENA region that showed increases in the age-standardised prevalence, incidence or YLD rates of LBP over the measurement period. Furthermore, in 2019 the number of prevalent cases were highest in the 35–39 age group, with males having a higher number of cases in all age groups. In addition, the age-standardised YLD rates for males in the MENA region were higher than the global estimates in almost all age groups, in both 1990 and 2019. Furthermore, the burden of LBP was not associated with the level of socio-economic development during the measurement period.

Conclusion

The burden attributable to LBP in the MENA region decreased slightly from 1990 to 2019. Furthermore, the burden among males was higher than the global average. Consequently, more integrated healthcare interventions are needed to more effectively alleviate the burden of low back pain in this region.
Teaching to transform surgical culture: an educational programme and thematic analysis in a general surgery department
Authors: Dave Madhav Sanatkumar , Mobarak Shahd , Tarazi Munir , Macutkiewicz Christian
Published: January 2023

Introduction

General surgery departments are busy, meaning educational opportunities may be sporadic. Clinical priorities can sometimes supersede teaching and trainees may feel alienated at the periphery of the working community. In this study, we demonstrate how a reflective, multidisciplinary general surgery teaching programme was established and use this to assess the impact of structured teaching on surgical doctors of all grades in the department.

Methods

Twelve semi-structured telephone interviews were conducted with participants of varying grades. Transcripts were analysed using a grounded theory thematic analysis, revealing four themes: the value of teaching; learning as a community; barriers to successful training; and culture of surgery.

Discussion

Teaching helped juniors construct healthy narratives around general surgery and encouraged a process of professional identity formation. Pairing junior and senior colleagues allowed both to develop their skills, and reflective learning revealed new learning opportunities. Transparency across the ‘community of practice’ was achieved and the programme helped juniors overcome negative stereotypes of intimidation embedded in the hidden surgical curriculum.

Conclusion

Reflective, multidisciplinary learning can challenge the hidden curriculum and encourage team cohesion. A commitment to critical reflective teaching will be vital in cultivating surgeons of the future.
Effectiveness of point of care ultrasound (POCUS) simulation course and skills retention for Japanese nurse practitioners
Authors: Yamada Toru , Ehara Jun , Funakoshi Hiraku , Endo Keita , Kitano Yuka
Published: January 2023

Background

In Japan, the nurse practitioner (NP) system has only been in place for a short time, and there is no ultrasound (US) simulation course for NPs. Therefore, NPs may have to attend US simulation courses for physicians. We evaluated whether US simulation course for physicians lead to improved image acquisition and interpretation amongst NPs and, if so, if these changes would be maintained over time.

Methods

A 2-day point-of-care ultrasound (POCUS) course designed for physicians in cardiac US, lung US, lower extremity deep vein thrombosis (DVT) US, and abdominal US was held for Japanese nurse practitioners (JNP) and JNP trainees in 2018 and 2019. Participants kept a record of the number of US examinations they performed for 3 months before and 3 months after the course. The number of US exams performed was grouped into six categories. All participants underwent pre-course, immediate post-course, and 4-month post-course testing to assess image interpretation skills, image acquisition skills, and confidence.

Results

Thirty-three participants from 21 facilities completed the program. Before and immediately after the course, test scores of the image interpretation test, image acquisition test, and confidence increased significantly (37.1, 72.6: P < 0.001), (13.7, 53.6: P < 0.001), and (15.8, 35.7: P < 0.001), respectively. Comparing the follow-up tests immediately after the course and 4 months later, there was no decrease in scores on the image interpretation test, the image acquisition test, or confidence (72.6, 71.8: P = 1.00) (53.6, 52.9: p = 1.00) (35.7, 33.0: P = 0.34). There was a statistically significant increase (P < 0.001) in both the total number of ultrasound examinations and in the number of ultrasound examinations by category (cardiac, lung, lower extremity DVT, and abdominal) in the 3 months before and 3 months after the course.

Conclusions

The POCUS simulation course for physicians is useful for JNPs to acquire US examination skills even if it is not arranged for JNPs. Image interpretation skill, image acquisition skill, and confidence improved significantly and were maintained even after 4 months of the course. It leads to behavioral changes such as increasing the number of US examinations in daily practice after the course.
Diagnosis of coronary artery disease in patients with type 2 diabetes mellitus based on computed tomography and pericoronary adipose tissue radiomics: a retrospective cross-sectional study
Authors: Dong Xiaolin , Li Na , Zhu Chentao , Wang Yujia , Shi Ke , Pan Hong , Wang Shuting , Shi Zhenzhou , Geng Yayuan , Wang Wei , Zhang Tong
Published: January 2023

Background

Patients with type 2 diabetes mellitus (T2DM) are highly susceptible to cardiovascular disease, and coronary artery disease (CAD) is their leading cause of death. We aimed to assess whether computed tomography (CT) based imaging parameters and radiomic features of pericoronary adipose tissue (PCAT) can improve the diagnostic efficacy of whether patients with T2DM have developed CAD.

Methods

We retrospectively recruited 229 patients with T2DM but no CAD history (146 were diagnosed with CAD at this visit and 83 were not). We collected clinical information and extracted imaging manifestations from CT images and 93 radiomic features of PCAT from all patients. All patients were randomly divided into training and test groups at a ratio of 7:3. Four models were constructed, encapsulating clinical factors (Model 1), clinical factors and imaging indices (Model 2), clinical factors and Radscore (Model 3), and all together (Model 4), to identify patients with CAD. Receiver operating characteristic curves and decision curve analysis were plotted to evaluate the model performance and pairwise model comparisons were performed via the DeLong test to demonstrate the additive value of different factors.

Results

In the test set, the areas under the curve (AUCs) of Model 2 and Model 4 were 0.930 and 0.929, respectively, with higher recognition effectiveness compared to the other two models (each p < 0.001). Of these models, Model 2 had higher diagnostic efficacy for CAD than Model 1 (p < 0.001, 95% CI [0.129–0.350]). However, Model 4 did not improve the effectiveness of the identification of CAD compared to Model 2 (p = 0.776); similarly, the AUC did not significantly differ between Model 3 (AUC = 0.693) and Model 1 (AUC = 0.691, p = 0.382). Overall, Model 2 was rated better for the diagnosis of CAD in patients with T2DM.

Conclusions

A comprehensive diagnostic model combining patient clinical risk factors with CT-based imaging parameters has superior efficacy in diagnosing the occurrence of CAD in patients with T2DM.
Echocardiographic reference ranges for noninvasive left ventricular 18-segment myocardial work index and work efficiency in a healthy Asian population
Authors: Wu Jian , Huang Xinyi , Huang Kunhui , Tang Yiruo , Gao Qiumei , Chen Xu , Jing Bo , Wang Xinyu , Lin Biqin , Su Maolong
Published: January 2023

Background

Left ventricular (LV) myocardial work index (WI) and work efficiency (WE) have become the latest indicators for assessing LV function. Reference ranges for normal LV segmental WI and WE have not been established.

Methods

Four hundred eleven healthy Asian subjects (47% men, median age: 35 years) were enrolled prospectively. WI and WE were analysed using the LV pressure–strain loop (LVPSL) with specific software.

Results

WI and WE differed significantly between segments as well as between walls and levels of the left ventricle. The anteroseptal basal segment had the lowest WI and WE (1440 mmHg ± 324 and 92% [88–96], respectively) among the eighteen segments. Significant WI and WE differences were found between sexes and age groups. No correlation was observed between age groups and the average WI of any wall or level in men, while the average WI of several different walls and levels in women showed significant differences between age groups. The average WI of most walls and levels increased with age in women. No correlation was found between age groups and the average WE of any wall or level in either men or women.

Conclusions

This study establishes the normal reference values of WI and WE of eighteen segments for clinical work and clinical experiments. There were significant differences in WI and WE between segments, levels, and walls of the normal left ventricle. Sex should be considered when analysing WI and WE. Age should be considered when analysing WI in women.

Graphical Abstract
Tumors after kidney transplantation: a population study
Authors: Ietto Giuseppe , Gritti Mattia , Pettinato Giuseppe , Carcano Giulio , Gasperina Daniela Dalla
Published: January 2023

One of the main causes of post-transplant-associated morbidity and mortality is cancer. The aims of the project were to study the neoplastic risk within the kidney transplant population and identify the determinants of this risk. A cohort of 462 renal transplant patients from 2010 to 2020 was considered. The expected incidence rates of post-transplant cancer development in the referenced population, the standardized incidence ratios (SIR) taking the Italian population as a comparison, and the absolute risk and the attributable fraction were extrapolated from these cohorts of patients. Kidney transplant recipients had an overall cancer risk of approximately three times that of the local population (SIR 2.8). A significantly increased number of cases were observed for Kaposi’s sarcoma (KS) (SIR 195) and hematological cancers (SIR 6.8). In the first 3 years post-transplant, the risk to develop either KS or hematological cancers was four times higher than in the following years; in all cases of KS, the diagnosis was within 2 years from the transplant. Post-transplant immunosuppression represents the cause of 99% of cases of KS and 85% of cases of lymphomas, while only 39% is represented by solid tumors. Data related to the incidence, the percentages attributable to post-transplant immunosuppression, and the time of onset of neoplasms, particularly for KS and hematological tumors could help improve the management for the follow-up in these patients.
The potential use of mesenchymal stem cells-derived exosomes as microRNAs delivery systems in different diseases
Authors: Oveili Elham , Vafaei Somayeh , Bazavar Haniyeh , Eslami Yeganeh , Mamaghanizadeh Ehsan , Yasamineh Saman , Gholizadeh Omid
Published: January 2023

MicroRNAs (miRNAs) are a group of small non-coding RNAs that regulate gene expression by targeting mRNA. Moreover, it has been shown that miRNAs expression are changed in various diseases, such as cancers, autoimmune disease, infectious diseases, and neurodegenerative Diseases. The suppression of miRNA function can be easily attained by utilizing of anti-miRNAs. In contrast, an enhancement in miRNA function can be achieved through the utilization of modified miRNA mimetics. The discovery of appropriate miRNA carriers in the body has become an interesting subject for investigators. Exosomes (EXOs) therapeutic efficiency and safety for transferring different cellular biological components to the recipient cell have attracted significant attention for their capability as miRNA carriers. Mesenchymal stem cells (MSCs) are recognized to generate a wide range of EXOs (MSC-EXOs), showing that MSCs may be effective for EXO generation in a clinically appropriate measure as compared to other cell origins. MSC-EXOs have been widely investigated because of their immune attributes, tumor-homing attributes, and flexible characteristics. In this article, we summarized the features of miRNAs and MSC-EXOs, including production, purification, and miRNA loading methods of MSC-EXOs, and the modification of MSC-EXOs for targeted miRNA delivery in various diseases.

Graphical abstract
Extracellular matrix stiffness mediates uterine repair via the Rap1a/ARHGAP35/RhoA/F-actin/YAP axis
Authors: Zhang Tao , Hu Ruiting , Wang Yan , Guo Shuai , Wu Zhimin , Liu Junfeng , Han Chunyang , Qiu Changwei , Deng Ganzhen
Published: January 2023

The integrity of the structure and function of the endometrium is essential for the maintenance of fertility. However, the repair mechanisms of uterine injury remain largely unknown. Here, we showed that the disturbance of mechanical cue homeostasis occurs after uterine injury. Applying a multimodal approach, we identified YAP as a sensor of biophysical forces that drives endometrial regeneration. Through protein activation level analysis of the combinatorial space of mechanical force strength and of the presence of particular kinase inhibitors and gene silencing reagents, we demonstrated that mechanical cues related to extracellular matrix rigidity can turn off the Rap1a switch, leading to the inactivation of ARHGAP35and then induced activation of RhoA, which in turn depends on the polymerization of the agonist protein F-actin to activate YAP. Further study confirmed that mechanotransduction significantly accelerates remodeling of the uterus by promoting the proliferation of endometrial stromal cells in vitro and in vivo. These studies provide new insights into the dynamic regulatory mechanisms behind uterine remodeling and the function of mechanotransduction.
Panomics reveals patient individuality as the major driver of colorectal cancer progression
Authors: Praus Friederike , Künstner Axel , Sauer Thorben , Kohl Michael , Kern Katharina , Deichmann Steffen , Végvári Ákos , Keck Tobias , Busch Hauke , Habermann Jens K. , Gemoll Timo
Published: January 2023

Background

Colorectal cancer (CRC) is one of the most prevalent cancers, with over one million new cases per year. Overall, prognosis of CRC largely depends on the disease stage and metastatic status. As precision oncology for patients with CRC continues to improve, this study aimed to integrate genomic, transcriptomic, and proteomic analyses to identify significant differences in expression during CRC progression using a unique set of paired patient samples while considering tumour heterogeneity.

Methods

We analysed fresh-frozen tissue samples prepared under strict cryogenic conditions of matched healthy colon mucosa, colorectal carcinoma, and liver metastasis from the same patients. Somatic mutations of known cancer-related genes were analysed using Illumina's TruSeq Amplicon Cancer Panel; the transcriptome was assessed comprehensively using Clariom D microarrays. The global proteome was evaluated by liquid chromatography-coupled mass spectrometry (LC‒MS/MS) and validated by two-dimensional difference in-gel electrophoresis. Subsequent unsupervised principal component clustering, statistical comparisons, and gene set enrichment analyses were calculated based on differential expression results.

Results

Although panomics revealed low RNA and protein expression of CA1, CLCA1, MATN2, AHCYL2, and FCGBP in malignant tissues compared to healthy colon mucosa, no differentially expressed RNA or protein targets were detected between tumour and metastatic tissues. Subsequent intra-patient comparisons revealed highly specific expression differences (e.g., SRSF3, OLFM4, and CEACAM5) associated with patient-specific transcriptomes and proteomes.

Conclusion

Our research results highlight the importance of inter- and intra-tumour heterogeneity as well as individual, patient-paired evaluations for clinical studies. In addition to changes among groups reflecting CRC progression, we identified significant expression differences between normal colon mucosa, primary tumour, and liver metastasis samples from individuals, which might accelerate implementation of precision oncology in the future.
Role of acyl-coenzyme A: cholesterol transferase 1 (ACAT1) in retinal neovascularization
Authors: Zaidi Syed A. H. , Lemtalsi Tahira , Xu Zhimin , Santana Isabella , Sandow Porsche , Labazi Leila , Caldwell Robert W. , Caldwell Ruth B. , Rojas Modesto A.
Published: January 2023

Background

We have investigated the efficacy of a new strategy to limit pathological retinal neovascularization (RNV) during ischemic retinopathy by targeting the cholesterol metabolizing enzyme acyl-coenzyme A: cholesterol transferase 1 (ACAT1). Dyslipidemia and cholesterol accumulation have been strongly implicated in promoting subretinal NV. However, little is known about the role of cholesterol metabolism in RNV. Here, we tested the effects of inhibiting ACAT1 on pathological RNV in the mouse model of oxygen-induced retinopathy (OIR).

Methods

In vivo studies used knockout mice that lack the receptor for LDL cholesterol (LDLR−/−) and wild-type mice. The wild-type mice were treated with a specific inhibitor of ACAT1, K604 (10 mg/kg, i.p) or vehicle (PBS) during OIR. In vitro studies used human microglia exposed to oxygen–glucose deprivation (OGD) and treated with the ACAT1 inhibitor (1 μM) or PBS.

Results

Analysis of OIR retinas showed that increased expression of inflammatory mediators and pathological RNV were associated with significant increases in expression of the LDLR, increased accumulation of neutral lipids, and formation of toxic levels of cholesterol ester (CE). Deletion of the LDLR completely blocked OIR-induced RNV and significantly reduced the AVA. The OIR-induced increase in CE formation was accompanied by significant increases in expression of ACAT1, VEGF and inflammatory factors (TREM1 and MCSF) (p < 0.05). ACAT1 was co-localized with TREM1, MCSF, and macrophage/microglia makers (F4/80 and Iba1) in areas of RNV. Treatment with K604 prevented retinal accumulation of neutral lipids and CE formation, inhibited RNV, and decreased the AVA as compared to controls (p < 0.05). The treatment also blocked upregulation of LDLR, ACAT1, TREM1, MCSF, and inflammatory cytokines but did not alter VEGF expression. K604 treatment of microglia cells also blocked the effects of OGD in increasing expression of ACAT1, TREM1, and MCSF without altering VEGF expression.

Conclusions

OIR-induced RNV is closely associated with increases in lipid accumulation and CE formation along with increased expression of LDLR, ACAT1, TREM1, and MCSF. Inhibiting ACAT1 blocked these effects and limited RNV independently of alterations in VEGF expression. This pathway offers a novel strategy to limit vascular injury during ischemic retinopathy.

Graphical Abstract
Elective adhesiolysis for chronic abdominal pain reduces long-term risk of adhesive small bowel obstruction
Authors: van den Beukel Barend A. W. , Toneman Masja K. , van Veelen Fleur , van Oud-Alblas Marjolein Blusse , van Dongen Koen , Stommel Martijn W. J. , van Goor Harry , ten Broek Richard P. G.
Published: January 2023

Background

Selected patients with adhesion-related chronic abdominal pain can be treated effectively by adhesiolysis with the application of adhesion barriers. These patients might also have an increased risk to develop adhesive small bowel obstruction (ASBO). It is unknown how frequently these patients develop ASBO, and how elective adhesiolysis for pain impacts the risk of ASBO.

Methods

Patients with adhesion-related chronic pain were included in this cohort study with long-term follow-up. The diagnosis of adhesions was confirmed using CineMRI. The decision for operative treatment of adhesions was made by shared agreement based on the correlation of complaints with CineMRI findings. The primary outcome was the 5-years incidence of readmission for ASBO. Incidence was compared between patients with elective adhesiolysis and those treated non-operatively and between patients with and without previous ASBO. Univariable and multivariable Cox regression analysis was performed to identify predictive factors for ASBO. Secondary outcomes included reoperation for ASBO and self-reported pain and other abdominal symptoms.

Results

A total of 122 patients were included, 69 patients underwent elective adhesiolysis. Thirty patients in both groups had previous episodes of ASBO in history. During 5-year follow-up, the readmission rate for ASBO was 6.5% after elective adhesiolysis compared to 26.9% after non-operative treatment (p = 0.012). These percentages were 13.3% compared to 40% in the subgroup of patients with previous episodes of ASBO (p = 0.039). In multivariable analysis, elective adhesiolysis was associated with a decreased risk of readmission for ASBO with an odds ratio of 0.21 (95% CI 0.07–0.65), the risk was increased in patients with previous episodes with a odds ratio of 19.2 (95% CI 2.5–144.4). There was no difference between the groups in the prevalence of self-reported abdominal pain. However, in surgically treated patients the impact of pain on daily activities was lower, and the incidence of other symptoms was lower.

Conclusion

More than one in four patients with chronic adhesion-related pain develop episodes of ASBO when treated non-operatively. Elective adhesiolysis reduces the incidence of ASBO in patients with chronic adhesion-related symptoms, both in patients with and without previous episodes of ASBO in history.

Trial registration The study was registered at Clinicaltrials.gov under NCT01236625.
An atlas of lamina-associated chromatin across twelve human cell types reveals an intermediate chromatin subtype
Authors: Shah Parisha P. , Keough Kathleen C. , Gjoni Ketrin , Santini Garrett T. , Abdill Richard J. , Wickramasinghe Nadeera M. , Dundes Carolyn E. , Karnay Ashley , Chen Angela , Salomon Rachel E. A. , Walsh Patrick J. , Nguyen Son C. , Whalen Sean , Joyce Eric F. , Loh Kyle M. , Dubois Nicole , Pollard Katherine S. , Jain Rajan
Published: January 2023

Background

Association of chromatin with lamin proteins at the nuclear periphery has emerged as a potential mechanism to coordinate cell type-specific gene expression and maintain cellular identity via gene silencing. Unlike many histone modifications and chromatin-associated proteins, lamina-associated domains (LADs) are mapped genome-wide in relatively few genetically normal human cell types, which limits our understanding of the role peripheral chromatin plays in development and disease.

Results

To address this gap, we map LAMIN B1 occupancy across twelve human cell types encompassing pluripotent stem cells, intermediate progenitors, and differentiated cells from all three germ layers. Integrative analyses of this atlas with gene expression and repressive histone modification maps reveal that lamina-associated chromatin in all twelve cell types is organized into at least two subtypes defined by differences in LAMIN B1 occupancy, gene expression, chromatin accessibility, transposable elements, replication timing, and radial positioning. Imaging of fluorescently labeled DNA in single cells validates these subtypes and shows radial positioning of LADs with higher LAMIN B1 occupancy and heterochromatic histone modifications primarily embedded within the lamina. In contrast, the second subtype of lamina-associated chromatin is relatively gene dense, accessible, dynamic across development, and positioned adjacent to the lamina. Most genes gain or lose LAMIN B1 occupancy consistent with cell types along developmental trajectories; however, we also identify examples where the enhancer, but not the gene body and promoter, changes LAD state.

Conclusions

Altogether, this atlas represents the largest resource to date for peripheral chromatin organization studies and reveals an intermediate chromatin subtype.
Update to the study protocol Face Your Fears: Virtual reality-based cognitive behavioral therapy (VR-CBT) versus standard CBT for paranoid ideations in patients with schizophrenia spectrum disorders: a randomized clinical trial
Authors: Jeppesen U. N. , Due A. S. , Mariegaard L. , Pinkham A. , Vos M. , Veling W. , Nordentoft M. , Glenthøj L. B.
Published: January 2023

We unfortunately need to make an update to our published study protocol that describes a significant change in the design of the study. The Committee on Health Research Ethics of the Capital Region Denmark recently rejected the approval of changing the primary outcome in the trial, on the invariable grounds that the trial has already commenced. It is therefore necessary to retain the Green Paranoid Thought Scale (GPTS) part B, ideas of persecution, as our primary outcome, and GPTS part A, ideas of social reference, as a secondary outcome, which is described opposite in our published study protocol. The exchange of outcomes has not affected participation in our trial or the informed consent. Intervention in both groups and assessments are unchanged. The two outcomes together constitute GPTS and the unifying concept we attempt to treat, namely paranoid ideations. As this is a blinded, methodologically rigorous trial, we did not have—and still do not have—access to preliminary data, and therefore, we have no knowledge of the distribution of our two intervention groups nor the potential effect of the intervention. The power calculation remains unchanged irrespective of the selection of the primary outcome. We have been fully transparent with the changes in primary and secondary outcomes on ClinicalTrials.gov throughout the trial. Due to the considerations mentioned above, we assumed that there would not be any ethical implications of the change of primary outcome. We sincerely apologize for the irregularity caused because of this assumption.

Trial registration

ClinicalTrials.gov NCT04902066. Initial release April 19th, 2021.