bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive in silico analysis of the underutilized crop tef (Eragrostis tef (Zucc.) Trotter) genome reveals drought tolerance signatures
Authors: Bekele-Alemu Abreham , Ligaba-Osena Ayalew
Published: October 2023

Background

Tef (Eragrostis tef) is a C4 plant known for its tiny, nutritious, and gluten-free grains. It contains higher levels of protein, vitamins, and essential minerals like calcium (Ca), iron (Fe), copper (Cu), and zinc (Zn) than common cereals. Tef is cultivated in diverse ecological zones under diverse climatic conditions. Studies have shown that tef has great diversity in withstanding environmental challenges such as drought. Drought is a major abiotic stress severely affecting crop productivity and becoming a bottleneck to global food security. Here, we used in silico-based functional genomic analysis to identify drought-responsive genes in tef and validated their expression using quantitative RT-PCR.

Results

We identified about 729 drought-responsive genes so far reported in six crop plants, including rice, wheat, maize, barley, sorghum, pearl millet, and the model plant Arabidopsis, and reported 20 genes having high-level of GO terms related to drought, and significantly enriched in several biological and molecular function categories. These genes were found to play diverse roles, including water and fluid transport, resistance to high salt, cold, and drought stress, abscisic acid (ABA) signaling, de novo DNA methylation, and transcriptional regulation in tef and other crops. Our analysis revealed substantial differences in the conserved domains of some tef genes from well-studied rice orthologs. We further analyzed the expression of sixteen tef orthologs using quantitative RT-PCR in response to PEG-induced osmotic stress.

Conclusions

The findings showed differential regulation of some drought-responsive genes in shoots, roots, or both tissues. Hence, the genes identified in this study may be promising candidates for trait improvement in crops via transgenic or gene-editing technologies.
Propofol TCI or sevoflurane anesthesia without muscle relaxant for thoracoscopic thymectomy in myasthenia gravis patients: a prospective, observational study
Authors: Hien Vo Van , Tu Nguyen Huu , Thu Nguyen Dang
Published: October 2023

Background

Myasthenia gravis (MG) patients interact unpredictably with anesthetic agents, including neuromuscular blocking agents. Here, we investigate the effectiveness of general anesthesia without muscle relaxants using either propofol via target-controlled infusion systems (TCI) or sevoflurane in MG patients undergoing thoracoscopic thymectomy.

Methods

This prospective, open-label, observational study was conducted in a university hospital. We included 90 myasthenic patients undergoing thoracoscopic thymectomy with general anesthesia. Patients received induction and maintenance anesthesia with propofol TCI (group P, n = 45) or induction with propofol 2–3 mg.kg−1 and maintenance anesthesia with sevoflurane (group S, n = 45). In both groups, the procedure was performed under the guidance of entropy with sufentanil but not a muscle relaxant. Intubation conditions, hemodynamic changes, respiratory function, neuromuscular transmission, arterial blood gas, and complications were evaluated.

Results

All patients achieved good intubation conditions. Hemodynamic instability was more frequent in group S than in group P, mostly in the induction stage, and was controllable. The reduction in the intraoperative train-of-four ratio from baseline at 30 min, 60 min, and 90 min in group S was 10.3%, 14.2%, and 14.3%, respectively, significantly higher than that in group P (6.8%, 7.2%, and 8.4%, respectively), which completely recovered at the end of the surgery. All patients were extubated in the operating room without complications. No other significant differences between the groups were observed.

Conclusions

Anesthesia with propofol TCI or sevoflurane without muscle relaxants in MG patients offered safe and effective conditions for thoracoscopic thymectomy. Sevoflurane achieved higher levels of intraoperative muscular relaxation than propofol TCI. Postoperative neuromuscular function was not affected by these anesthetics.
Reasons for missing evidence in rehabilitation meta-analyses: a cross-sectional meta-research study
Authors: Lazzarini Stefano Giuseppe , Stella Yousif Marzia , Bargeri Silvia , Castellini Greta , Gianola Silvia
Published: October 2023

Background

Systematic reviews of randomized controlled trials are the best evidence for informing on intervention effectiveness. Their results, however, can be biased due to omitted evidence in the quantitative analyses. We aimed to assess the proportion of randomized controlled trials omitted from meta-analyses in the rehabilitation field and explore related reasons.

Methods

This is a cross-sectional meta-research study. For each systematic review included in a published selected sample in the rehabilitation field, we identified an index meta-analysis on the primary outcome and the main comparison. We then looked at all the studies considered eligible for the chosen comparison in the systematic review and identified those trials that have been omitted (i.e., not included) from each index meta-analysis. Reasons for omission were collected based on an eight-reason classification. We used descriptive statistics to describe the proportion of omitted trials overall and according to each reason.

Results

Starting from a cohort of 827 systematic reviews, 131 index meta-analyses comprising a total of 1761 eligible trials were selected. Only 16 index meta-analyses included all eligible studies while 15 omitted studies without providing references. From the remaining 100 index meta-analyses, 717 trials (40,7%) were omitted overall. Specific reasons for omission were: "unable to distinguish between selective reporting and inadequate planning" (39,3%, N = 282), "inadequate planning" (17%, N = 122), "justified to be not included" (15,1%, N = 108), "incomplete reporting" (8,4%, N = 60), "selective reporting" (3,3%, N = 24) and other situations (e.g., outcome present but no motivation for omission) (5,2%, N = 37). The 11,7% (N = 84) of omitted trials were not assessed due to non-English language or full text not available.

Conclusions

Almost half of the eligible trials were omitted from their index meta-analyses. Better reporting, protocol registration, definition and adoption of core outcome sets are needed to prevent omission of evidence in systematic reviews.
Are primary care consultations in Trinidad patient-centered? A cross-sectional study of patients with non-communicable diseases
Authors: Rahaman Reisa R , Motilal M Shastri , Khan Raveed , Maharaj Rohan G
Published: October 2023

Background

The aim of this study was to measure the patient’s perception of patient centeredness in their consultations for non-communicable diseases (NCDs). We also measured consultation length and patient enablement.

Method

A cross-sectional study was conducted over 2 months at four primary care clinics at the St. Joseph cluster of the North Central Regional Health Authority (NCRHA) in Trinidad and Tobago. Interviewers timed the consultation and completed post-consultation questionnaires using the Patient Perception of Patient-Centeredness (PPPC) questionnaire and the Patient Enablement Index (PEI). The PPPC is a 14-item (each scored 1–4) Likert-scaled instrument. The total score is averaged and a PPPC score of 4 is the maximum. The PEI measures the ability of the patient to cope with life and their disease. The PEI consists of 6 questions scored 0–2, with a maximum score of 12.

Results

There were 180 respondents (response rate = 82.5%). Participants were female (75.6%), aged over 65 years (50.6%), married (51.1%), Indo-Trinidadian (52.2%), and Christian (60.6%). Half achieved a primary school education, and 37.2% secondary. The consultation length ranged between 1.32 and 31.22 min. The average, median and mode of the consultation length were 8.5, 7.74 and 10 min, respectively. The average, median and mode of the measures of patient-centeredness were PPPC (3.67, 3.86 and 4) and PEI score (5.93, 6 and 6). The PPPC average was lower in patients with a stroke (p = 0.022), and higher among those with more than 2 consultation interruptions (p = 0.015) and those who knew the doctor very well (p = 0.015). The PEI score was lower in patients with heart disease (p = 0.022). The consultation length was longer in those with tertiary education (p = 0.044) and those with two consultation interruptions (p = 0.032). PPPC Average and PEI Score correlated well (ρ = 0.408, p < 0.001). The consultation length correlated with the PPPC Average (ρ = 0.168,p = 0.025).

Conclusion

Primary Care consultations in this cluster of health centres in NCRHA in Trinidad were often patient centered. The consultation length, patient-centeredness, measured with the PPPC instrument, and patient enablement scores, measured with the PEI instrument, in consultations for NCDs in Trinidad compare favourably with international reports.
The utility of self-expanding metal stents in benign biliary strictures- a retrospective case series
Authors: Mallette Katlin , Hawel Jeffrey , Elnahas Ahmad , Alkhamesi Nawar A. , Schlachta Christopher M. , Tang Ephraim S.
Published: October 2023

Background

Benign biliary strictures can have a significant negative impact on patient quality of life. There are several modalities which can be utilized with the goal of stricture resolution. These techniques include balloon dilatation, placement of multiple plastic stents and more recently, the use of metal stents. The aim of this study was to evaluate the local success of self-expanding metal stents in successfully resolving benign biliary strictures.

Methods

This was a single institution, retrospective case series. Patients included in our study were patients who underwent endoscopic retrograde cholangiopancreatography with placement of self expanding metal stents for benign biliary strictures at our institution between 2016–2022. Patients were excluded for the following: malignant stricture, and inability to successfully place metal stent. Data was evaluated using two-sided t-test with 95% confidence interval.

Results

A total of 31 patients underwent placement of 43 self-expanding metal stents and met inclusion criteria. Mean age of patients was 59 ± 10 years, and were largely male (74.2% vs. 25.8%). Most strictures were anastomotic stricture post liver transplant (87.1%), while the remainder were secondary to chronic pancreatitis (12.9%). Complications of stent placement included cholangitis (18.6%), pancreatitis (2.3%), stent migration (20.9%), and inability to retrieve stent (4.7%). There was successful stricture resolution in 73.5% of patients with anastomotic stricture and 33.3% of patients with stricture secondary to pancreatitis. Resolution was more likely if stent duration was > / = 180 days (73.3% vs. 44.4%, p < 0.05). There was no demonstrated added benefit when stent duration was > / = 365 days (75% vs. 60.9%, p = 0.64).

Conclusions

This study demonstrates that self expanding metal stents are a safe and effective treatment for benign biliary strictures, with outcomes comparable to plastic stents with fewer interventions. This study indicates that the optimal duration to allow for stricture resolution is 180–365 days.
Perfusion deficits in thrombolysis-treated acute ischemic stroke patients with negative or positive diffusion-weighted imaging
Authors: Zhu Cuiting , Qin Wei , Xu Jihua , Hu Wenli
Published: October 2023

Objective

Magnetic resonance imaging (MRI) and CT perfusion may provide diagnostic information for intravenous tissue-type plasminogen activator (IV t-PA) administration in acute ischemic stroke (AIS) patients. We aimed to compare the clinical features and perfusion deficits of diffusion weighted imaging (DWI)-negative and DWI-positive AIS patients.

Methods

This retrospective and observational study included thrombolysis-treated AIS patients undergoing multimodel CT imaging before treatment and DWI after treatment between 2021 and 2022. Two experienced neuroradiologists blindly and independently examined the images to identify perfusion deficits in AIS patients. The patients were divided into DWI-positive and DWI-negative groups based on visible hyperintense lesions on DWI. A modified Rankin scale (mRS) score of ≤ 2 indicated good functional outcomes at discharge. Sensitivity analysis was conducted to determine whether CT perfusion was an independent predictor of positive DWI imaging on follow-up.

Results

This study included 151 patients, of whom 35 (23.2%) patients were DWI-negative on follow-up. These DWI-negative patients were less likely to have a medical history of atrial fibrillation; they had lower triglyceride levels, a shorter admission time, lower National Institutes of Health Stroke Scale (NIHSS) scores after IV t-PA and lower mRS scores at discharge, and had better functional outcomes. A total of 37.1% of DWI-positive and 25.7% of DWI-negative patients had vascular stenosis (P = 0.215). A total of 47.4% of DWI-positive and 37.1% of DWI-negative patients had CT perfusion deficits (P = 0.284). A total of 73.5% of patients with normal CT perfusion had positive DWI, while 19.1% of patients with perfusion deficits had negative DWI. The sensitivity and specificity of NCCT were 14.8% and 97.1% (Kappa = 0.061, P = 0.074), CTP was 47.4% and 62.9% for predicting DWI lesion (Kappa = 0.069, P = 0.284).

Conclusions

About 23.2% of AIS patients who received intravenous thrombolysis treatment did not have a relevant DWI-MRI lesion on follow-up. Over one-third of patients in the DWI-MRI negative group showed CT perfusion deficits, with a sensitivity of 47.4% for predicting DWI lesions in non-mechanical thrombectomy patients.
Skin-to-skin contact for the prevention of neonatal hypoglycaemia: a systematic review and meta-analysis
Authors: Lord Libby G. , Harding Jane E. , Crowther Caroline A. , Lin Luling
Published: October 2023

Background

Skin-to-skin contact between mother and infant after birth is recommended to promote breastfeeding and maternal-infant bonding. However, its impact on the incidence of neonatal hypoglycaemia is unknown. We conducted a systematic review and meta-analysis to assess this.

Methods

Published randomised control trials (RCTs), quasi-RCTs, non-randomised studies of interventions, cohort, or case–control studies with an intervention of skin-to-skin care compared to other treatment were included without language or date restrictions. The primary outcome was neonatal hypoglycaemia (study-defined). We searched 4 databases and 4 trial registries from inception to May 12th, 2023. Quality of studies was assessed using Cochrane Risk of Bias 1 or Effective Public Health Practice Project Quality Assessment tools. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results were synthesised using RevMan 5.4.1 or STATA and analysed using random-effects meta-analyses where possible, otherwise with direction of findings tables. This review was registered prospectively on PROSPERO (CRD42022328322).

Results

This review included 84,900 participants in 108 studies, comprising 65 RCTs, 16 quasi-RCTs, seven non-randomised studies of intervention, eight prospective cohort studies, nine retrospective cohort studies and three case–control studies. Evidence suggests skin-to-skin contact may result in a large reduction in the incidence of neonatal hypoglycaemia (7 RCTs/quasi-RCTs, 922 infants, RR 0.29 (0.13, 0.66), p < 0.0001, I2 = 47%). Skin-to-skin contact may reduce the incidence of admission to special care or neonatal intensive care nurseries for hypoglycaemia (1 observational study, 816 infants, OR 0.50 (0.25–1.00), p = 0.050), but the evidence is very uncertain. Skin-to-skin contact may reduce duration of initial hospital stay after birth (31 RCTs, 3437 infants, MD -2.37 (-3.66, -1.08) days, p = 0.0003, I2 = 90%, p for Egger’s test = 0.02), and increase exclusive breastmilk feeding from birth to discharge (1 observational study, 1250 infants, RR 4.30 (3.19, 5.81), p < 0.0001), but the evidence is very uncertain.

Conclusion

Skin-to-skin contact may lead to a large reduction in the incidence of neonatal hypoglycaemia. This, along with other established benefits, supports the practice of skin-to-skin contact for all infants and especially those at risk of hypoglycaemia.
eHealth usage among parents to premature or surgically treated neonates: associations with eHealth literacy, healthcare satisfaction or satisfaction with an eHealth device
Authors: Derwig Mariette , Lindkvist Rose-Marie , Hallström Inger Kristensson , Johnsson Björn A. , Stenström Pernilla
Published: October 2023

Background

A specific eHealth device, a surf tablet, was developed for bridging between advanced in-hospital care and children’s homes. Since little is known about determinators for parental eHealth usage, the study’s aim was to explore if parents’ usage of the device was associated with their eHealth literacy, or their satisfaction with their child’s healthcare or with the specific surf tablet.

Methods

In this explorative usage and questionnaire study, parents to neonates who were discharged home after advanced in-hospital care were included. Their surf tablet usage at maximum 30 days after discharge was reported as frequency (%) of active days (usage days/days having the device) and median number of tablet activities (chat and photo) per usage day. eHealth literacy (eHealth Literacy Questionnaire; eHLQ), healthcare satisfaction (PedsQL Healthcare Satisfaction Generic Module), and satisfaction with the surf tablet were explored regarding tablet usage. Statistics were described in median (range) and (%) using non-parametric and regression models (p < 0.05).

Results

Parents to 32 children (11 premature, 21 operated) were included. Active days with eHealth communication using the device was 39% (9.0/29.5), with 2.0 (1.0-4.2) usage occasions per active day. Activity on the tablet was higher among parents reporting to be very satisfied or satisfied with the device (n = 25) compared with neutral/dissatisfied parents (n = 7) (2.8 vs. 2.2 vs. 1.6 activities) (p = 0.030), while their frequency of active days did not differ (31.6% vs. 38.3% vs. 40%) (p = 0.963). A higher eHealth literacy was not associated with frequency of active days (0.926 (0.652–1.317); p = 0.659) or number of eHealth activities (0.973 (0.758–1.250); p = 0.825). Healthcare satisfaction was not associated with higher frequency of active days 0.996 (0.983–1.009; p = 0.519); neither was number of eHealth activities 1.001 (0.991–1.011; p = 0.883).

Conclusion

In this study, eHealth usage was associated with parental satisfaction with the specific eHealth device, but not with eHealth literacy or healthcare satisfaction. To assure equal access to healthcare when using eHealth, the user-friendliness of the device seems to be crucial, and technical support needs to be in place.

ClinicalTrials.gov registration identifier

NCT04150120 (04/11/2019).
Could parental awareness of DBR influence youth off-campus sports? Test of a conditional process model
Authors: Tan Shuying , Lou Hu , Liu Xue , Chen Jin
Published: October 2023

Background

The “Double Reduction” policy published in China provides a new opportunity to increase youth sports. Based on the perspective of parents’ influence on their children, this study aimed to explore the impact of parental awareness of the “Double Reduction” policy on youth off-campus sports.

Methods

This study was conducted empirically through a nationwide sample survey to analyze the relationship between parental awareness of the “Double Reduction” policy, parental education anxiety, and parental attitudes toward children’s participation in sports and youth off-campus sports to construct and verify a conditional process model.

Results

Parental awareness of the “Double Reduction” policy had a significant positive impact on their children’s off-campus sports (β = 0.103, SE = 0.018, P < 0.01), but had a significant negative impact on parental education anxiety (β = -0.305, SE = 0.032, P < 0.01) which showed a significant negative effect on their children’s off-campus sports (β = -0.114, SE = 0.011, P < 0.01) and played a significant intermediary role between parental awareness of the “Double Reduction” policy and children’s off-campus sports (β = 0.031, 95%CI: 0.020 ~ 0.044). All dimensions of parental education anxiety showed different characteristics with only academic achievement anxiety (β = 0.034, 95%CI: 0.021 ~ 0.047), parent–child interaction anxiety (β = 0.027, 95%CI: 0.014 ~ 0.038), and learning attitude anxiety (β = 0.024, 95%CI: 0.015 ~ 0.033) presenting significant mediating effects. The interaction between parental education anxiety and parental attitudes toward children’s sports significantly positively impacted youth off-campus sports (β = 0.008, SE = 0.001, P < 0.01). The moderating role of parental attitudes toward their children’s participation in off-campus sports, indicating it was significant (95%CI: 0.005 ~ 0.011) along the pathway of parental awareness of the “Double Reduction” policy to parental education anxiety to youth off-campus sports.

Conclusions

Parental awareness of the “Double Reduction” policy has a positive impact on youth off-campus sports. Parents’ anxiety about their children’s academic achievement, parent–child interaction anxiety, and learning attitude anxiety mediate in the process model. Parental attitudes toward sports can magnify the relationship between their education anxiety and youth off-campus sports.
Efficacy and safety of remimazolam besilate for sedation in outpatients undergoing impacted third molar extraction: a prospective exploratory study
Authors: Oue Kana , Oda Aya , Shimizu Yoshitaka , Takahashi Tamayo , Kamio Hisanobu , Sasaki Utaka , Imamura Serika , Imado Eiji , Mukai Akari , Doi Mitsuru , Sakuma Miyuki , Ono Shigehiro , Aikawa Tomonao , Yoshida Mitsuhiro
Published: October 2023

Background

Dental treatments often cause anxiety, fear, and stress in patients. Intravenous sedation is widely used to alleviate these concerns, and various agents are employed for sedation. However, it is important to find safer and more effective sedation agents, considering the adverse effects associated with current agents. This study aimed to investigate the efficacy and safety of remimazolam besilate (hereinafter called “remimazolam”) and to determine the optimal dosages for sedation in outpatients undergoing dental procedures.

Methods

Thirty-one outpatients aged 18–65 years scheduled for impacted third molar extraction were included in the study. Remimazolam was administered as a single dose of 0.05 mg/kg followed by a continuous infusion at a rate of 0.35 mg/kg/h, with the infusion rate adjusted to maintain a sedation level at a Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) score of 2–4. The primary endpoint was the sedation success rate with remimazolam monotherapy, and the secondary endpoints included induction time, recovery time, time until discharge, remimazolam dose, respiratory and circulatory dynamics, and frequency of adverse events.

Results

The sedation success rate with remimazolam monotherapy was 100%. The remimazolam induction dose was 0.08 (0.07–0.09) mg/kg, and the anesthesia induction time was 3.2 (2.6–3.9) min. The mean infusion rate of remimazolam during the procedure was 0.40 (0.38–0.42) mg/kg/h. The time from the end of remimazolam administration to awakening was 8.0 (6.7–9.3) min, and the time from the end of remimazolam administration to discharge was 14.0 (12.5–15.5) min. There were no significant respiratory or circulatory effects requiring intervention during sedation.

Conclusions

Continuous intravenous administration of remimazolam can achieve optimal sedation levels without significantly affecting respiratory or circulatory dynamics. The study also provided guidance on the appropriate dosage of remimazolam for achieving moderate sedation during dental procedures. Additionally, the study findings suggest that electroencephalogram monitoring can be a reliable indicator of the level of sedation during dental procedural sedation with remimazolam.

Trial registration

The study was registered in the Japan Registry of Clinical Trials (No. jRCTs061220052) on 30/08/2022.
Is there an association between molar incisor hypomineralization and developmental dental anomalies? A case-control study
Authors: Şen Yavuz Betül , Sezer Berkant , Kaya Remziye , Tuğcu Nihan , Kargül Betül
Published: October 2023

Background

The aim of this study was to determine whether there is any association between molar incisor hypomineralization and developmental dental anomalies.

Methods

Two pediatric dentists evaluated panoramic radiographs of 429 children aged 8–14 years with molar incisor hypomineralization (study group) and 437 children without molar incisor hypomineralization (control group) in terms of developmental dental anomalies. Twelve different developmental dental anomalies were categorized into four types: size (microdontia, macrodontia); position (ectopic eruption of maxillary permanent first molars, infraocclusion of primary molars); shape (fusion, gemination, dilaceration, taurodontism, peg-shaped maxillary lateral incisors); and number (hypodontia, oligodontia, hyperdontia) anomalies.

Results

No significant difference was observed in the frequencies of developmental dental anomalies between the study and control groups in total, females, and males (p > 0.05). A statistically significant difference was found between the distribution of developmental size, position, shape, and number anomalies between the study and control groups (p = 0.024). The most common anomaly in both groups was hypodontia (6.3% and 5.9%, respectively). There was a significant difference between the study and control groups in terms of subtypes of shape anomaly in all children and females (p = 0.045 and p = 0.05, respectively).

Conclusions

While a significant difference was observed between the distributions of types of developmental dental anomalies between individuals with and without molar incisor hypomineralization, there was no difference in terms of the frequency of developmental dental anomalies.
Relatives’ experiences of care encounters in the general ward after ICU discharge: a qualitative study
Authors: Gyllander Theresa , Näppä Ulla , Häggström Marie
Published: October 2023

Background

Care encounters at general wards have many reasons, and the complexity differs. Some arriving at the ward are relatives of discharged intensive care unit patients’, who are usually more fragile than others due to what had happened to them. Research indicates that care encounters leave relatives dissatisfied. There is a lack of studies describing how relatives of adult patients experience the transfer from the intensive care unit.

Aim

The purpose of this study was to describe relatives’ experiences of care encounters with nurses during their loved ones’ stay in the general ward after being discharged from the intensive care unit.

Methods

A qualitative descriptive design with an inductive approach was used. Semi-structured individual interviews were conducted with relatives [n = 14) of patients from different hospitals in Sweden. Data were analysed using content analysis.

Results

Relatives expressed feeling a huge responsibility for ensuring the quality of care for their loved ones. It was essential to encounter available, committed, and compassionate nurses in the general ward after being transferred from the intensive care unit. The theme ‘longing for trust and struggling to be involved in their loved one’s care’ was illustrated in the two subthemes of ‘wanting to be seen as an important piece of the puzzle’ and ‘being vigilant and worrying about the quality of care’.

Conclusion

The relatives of patients experience their needs as unfulfilled in care encounters with nurses at the general ward after transfer from ICU. In order to meet the needs of relatives, nurses require well-developed non-technical skills to establish a compassionate interaction founded on trust and respect for the individual. Future research should investigate how relatives’ needs can be met in practice. New nursing innovations are necessary to structure encounters with patients and relatives transitioning from the intensive care unit.
Monitoring the immune response of macrophages in tuberculous granuloma through the expression of CD68, iNOS and HLA-DR in naturally infected beef cattle
Authors: Hamed Mohamed G. , Gómez-Laguna Jaime , Larenas-Muñoz Fernanda , Mahmoud Abdelzaher Z. , Ali Fatma Abo Zakaib , Abd-Elghaffar Sary Kh.
Published: October 2023

Bovine tuberculosis still represents a universal threat that creates a wider range of public and animal health impacts. One of the most important steps in the pathogenesis of this disease and granuloma formation is the phagocytosis of tuberculous bacilli by macrophages. Mycobacteria replicate in macrophages, which are crucial to the pathophysiology of mycobacterial infections; however, scarce information is available about the dynamics of the granuloma-stage immunological response. Therefore, immunohistochemistry was used in this work to evaluate the expression of CD68, iNOS, and HLA-DR in different stages of TB granulomas from naturally infected cattle with tuberculosis. Two thousand, one hundred and fifty slaughtered beef cattle were examined during the period from September 2020 to March 2022. Sixty of them showed gross tuberculous pulmonary lesions and samples were collected from all of them for histopathological examination, Ziehl-Neelsen (ZN) staining, and bacteriological culturing. Selected samples that yielded a positive result for ZN and mycobacterial culturing were subjected to an immunohistochemical study of CD68, iNOS, and HLA-DR expression by macrophages according to granuloma stages. Immunohistochemical analysis revealed that the immunolabeling of CD68+, iNOS+, and HLA-DR+ macrophages significantly reduced as the stage of granuloma increased from stage I to stage IV (P < 0.003, P < 0.002, and P < 0.002, respectively). The distribution of immunolabeled macrophages was similar for the three markers, with immunolabeled macrophages distributed throughout early-stage granulomas (I, II), and surrounding the necrotic core in late-stage granulomas (III, IV). Our results suggest a polarization to the pro-inflammatory environment and increased expression of CD68+, iNOS+, and HLA-DR+ macrophages in the early stages of granulomas (I, II), which may play a protective role in the immune response of naturally infected beef cattle with tuberculosis.
Construction of ceRNA prognostic model based on the CCR7/CCL19 chemokine axis as a biomarker in breast cancer
Authors: Ma Rufei , Guan Xiuliang , Teng Nan , Du Yue , Ou Shu , Li Xiaofeng
Published: October 2023

Background

The study of CCR7/CCL19 chemokine axis and breast cancer (BC) prognosis and metastasis is a current hot topic. We constructed a ceRNA network and risk-prognosis model based on CCR7/CCL19.

Methods

Based on the lncRNA, miRNA and mRNA expression data downloaded from the TCGA database, we used the starbase website to find the lncRNA and miRNA of CCR7/CCL19 and established the ceRNA network. The 1008 BC samples containing survival data were divided into Train group (504 cases) and Test group (504 cases) using R “caret” package. Then we constructed a prognostic risk model using RNA screened by univariate Cox analysis in the Train group and validated it in the Test and All groups. In addition, we explored the correlation between riskScores and clinical trials and immune-related factors (22 immune-infiltrating cells, tumor microenvironment, 13 immune-related pathways and 24 HLA genes). After transfection with knockdown CCR7, we observed the activity and migration ability of MDA-MB-231 and MCF-7 cells using CCK8, scratch assays and angiogenesis assays. Finally, qPCR was used to detect the expression levels of five RNAs in the prognostic risk model in MDA-MB-231 and MCF-7 cell.

Results

Patients with high expression of CCR7 and CCL19 had significantly higher overall survival times than those with low expression. The ceRNA network is constructed by 3 pairs of mRNA-miRNA pairs and 8 pairs of miRNA-lncRNA. After multivariate Cox analysis, we obtained a risk prognostic model: riskScore= -1.544 *`TRG-AS1`+ 0.936 * AC010327.5 + 0.553 *CCR7 -0.208 *CCL19 -0.315 *`hsa-let-7b-5p. Age, stage and riskScore can all be used as independent risk factors for BC prognosis. By drug sensitivity analysis, we found 5 drugs targeting CCR7 (convolamine, amikacin, AH-23,848, ondansetron, flucloxacillin). After transfection with knockdown CCR7, we found a significant reduction in cell activity and migration capacity in MDA-MB-231 cells.

Conclusion

We constructed the first prognostic model based on the CCR7/CCL19 chemokine axis in BC and explored its role in immune infiltration, tumor microenvironment, and HLA genes.
Complete spectrum of adverse events associated with chimeric antigen receptor (CAR)-T cell therapies
Authors: Yang Chieh , Nguyen John , Yen Yun
Published: October 2023

Chimeric antigen receptor (CAR)-T cell therapies have been approved by FDA to treat relapsed or refractory hematological malignancies. However, the adverse effects of CAR-T cell therapies are complex and can be challenging to diagnose and treat. In this review, we summarize the major adverse events, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and CAR T-cell associated HLH (carHLH), and discuss their pathophysiology, symptoms, grading, and diagnosis systems, as well as management. In a future outlook, we also provide an overview of measures and modifications to CAR-T cells that are currently being explored to limit toxicity.
Triglyceride-glucose index is associated with recurrent revascularization in patients with type 2 diabetes mellitus after percutaneous coronary intervention
Authors: Chen Qiang , Xiong Shiqiang , Zhang Zhen , Yu Xiuqiong , Chen Yingzhong , Ye Tao , Yang Siqi , Qi Lingyao , Chen Xu , Liu Hanxiong , Zheng Jingang , Cai Lin
Published: October 2023

Background

The Triglyceride-glucose (TyG) index, as a surrogate marker of insulin resistance, is independently associated with the severity of coronary artery lesions and the prognosis of coronary heart disease. The investigation aimed to explore the relationship between the TyG index and recurrent revascularization in individuals with type 2 diabetes mellitus (T2DM) resulting from the progression of lesions or in-stent restenosis (ISR) after percutaneous coronary intervention (PCI).

Method

A total of 633 patients who met the inclusion and exclusion criteria were enrolled and divided into three groups based on the tertiles of the TyG index. The primary endpoint was recurrent revascularization resulting from the progression of lesions or ISR. All-cause death was considered as the competing risk event. Competing risk analysis and Cox regression analysis for predicting recurrent revascularization after PCI were conducted stepwise. Variables were standardized to make the hazard ratio (HR), subdistribution hazard ratio (SHR) and corresponding 95% CI more consistent prior to being used for fitting the multivariate risk model. The predictive ability of the TyG index was evaluated using several measures, including the ROC curve, likelihood ratio test, Akaike’s information criteria, category-free continuous net reclassification improvement (cNRI > 0), and integrated discrimination improvement (IDI). Internal validation was conducted through bootstrapping with 1000 resamples.

Results

During a median follow-up period of 18.33 months, a total of 64 (10.11%) patients experienced recurrent revascularization, including 55 cases of lesion progression and 9 cases of in-stent restenosis. After controlling for competitive risk events, the TyG index was independently associated with a higher risk of recurrent revascularization [SHR:1.4345, (95% CI 1.1458–1.7959), P = 0.002]. The likelihood ratio test and Akaike’s information criteria showed that the TyG index significantly improves the prognostic ability. Additionally, adding the TyG index improved the ability of the established risk model in predicting recurrent revascularization, indicated by a C-index of 0.759 (95% CI 0.724–0.792, P < 0.01), with a cNRI > 0 of 0.170 (95% CI 0.023–0.287, P < 0.05), and an IDI of 0.024 (95% CI 0.009–0.039, P = 0.002). These results remained consistent when the models containing TyG index were confirmed using an internal bootstrap validation method.

Conclusion

The findings highlight the potential of the TyG index as a predictor of recurrent revascularization. Lesion progression emerged as the primary contributor to recurrent revascularization instead of in-stent restenosis. The incorporation of the TyG index into risk prediction models is likely to be beneficial for accurate risk stratification in order to improve prognosis.
Impact of stress hyperglycemia ratio on mortality in patients with critical acute myocardial infarction: insight from american MIMIC-IV and the chinese CIN-II study
Authors: Liu Jin , Zhou Yang , Huang Haozhang , Liu Rui , Kang Yu , Zhu Tingting , Wu Jielan , Gao Yuwei , Li Yuqi , Wang Chenyang , Chen Shiqun , Xie Nianjin , Zheng Xueyan , Meng Ruilin , Liu Yong , Tan Ning , Gao Fei
Published: October 2023

Background

Among patients with acute coronary syndrome and percutaneous coronary intervention, stress hyperglycemia ratio (SHR) is primarily associated with short-term unfavorable outcomes. However, the relationship between SHR and long-term worsen prognosis in acute myocardial infarction (AMI) patients admitted in intensive care unit (ICU) are not fully investigated, especially in those with different ethnicity. This study aimed to clarify the association of SHR with all-cause mortality in critical AMI patients from American and Chinese cohorts.

Methods

Overall 4,337 AMI patients with their first ICU admission from the American Medical Information Mart for Intensive Care (MIMIC)-IV database (n = 2,166) and Chinese multicenter registry cohort Cardiorenal ImprovemeNt II (CIN-II, n = 2,171) were included in this study. The patients were divided into 4 groups based on quantiles of SHR in both two cohorts.

Results

The total mortality was 23.8% (maximum follow-up time: 12.1 years) in American MIMIC-IV and 29.1% (maximum follow-up time: 14.1 years) in Chinese CIN-II. In MIMIC-IV cohort, patients with SHR of quartile 4 had higher risk of 1-year (adjusted hazard radio [aHR] = 1.87; 95% CI: 1.40–2.50) and long-term (aHR = 1.63; 95% CI: 1.27–2.09) all-cause mortality than quartile 2 (as reference). Similar results were observed in CIN-II cohort (1-year mortality: aHR = 1.44; 95%CI: 1.03–2.02; long-term mortality: aHR = 1.32; 95%CI: 1.05–1.66). In both two group, restricted cubic splines indicated a J-shaped correlation between SHR and all-cause mortality. In subgroup analysis, SHR was significantly associated with higher 1-year and long-term all-cause mortality among patients without diabetes in both MIMIC-IV and CIN-II cohort.

Conclusion

Among critical AMI patients, elevated SHR is significantly associated with and 1-year and long-term all-cause mortality, especially in those without diabetes, and the results are consistently in both American and Chinese cohorts.
Non-invasive detection of early microvascular changes in juveniles with type 1 diabetes
Authors: Bogusz-Górna Klaudia , Polańska Adriana , Dańczak-Pazdrowska Aleksandra , Żaba Ryszard , Sumińska Marta , Fichna Piotr , Kędzia Andrzej
Published: October 2023

Aims/Hypothesis

The study aimed to assess the usefulness of capillaroscopy and photoplethysmography in the search for early vascular anomalies in children with type 1 diabetes.

Methods

One hundred sixty children and adolescents aged 6–18, 125 patients with type 1 diabetes, and 35 healthy volunteers were enrolled in the study. We performed a detailed clinical evaluation, anthropometric measurements, nailfold capillaroscopy, and photoplethysmography.

Results

Patients with diabetes had more often abnormal morphology in capillaroscopy (68.60%, p = 0.019), enlarged capillaries (32.6%, p = 0.006), and more often more over five meandering capillaries (20.90%, p = 0.026) compared to healthy controls. Meandering capillaries correlated with higher parameters of nutritional status. In a photoplethysmography, patients with diagnosed neuropathy had a higher percentage of flow disturbance curves (p < 0.001) with a reduced frequency of normal curves (p = 0.050).

Conclusions

Capillaroscopic and photoplethysmographic examinations are non-invasive, painless, fast, and inexpensive. They are devoid of side effects, and there are no limitations in the frequency of their use and repetition. The usefulness of capillaroscopy and photoplethysmography in the study of microcirculation in diabetic patients indicates the vast application possibilities of these methods in clinical practice.
The MYBL2–CCL2 axis promotes tumor progression and resistance to anti-PD-1 therapy in ovarian cancer by inducing immunosuppressive macrophages
Authors: Pan Baoyue , Wan Ting , Zhou Yun , Huang Shuting , Yuan Linjing , Jiang Yinan , Zheng Xiaojing , Liu Pingping , Xiang Huiling , Ju Mingxiu , Luo Rongzhen , Jia Weihua , Lan ChunYan , Li Jundong , Zheng Min
Published: October 2023

Background

An immunosuppressive tumor microenvironment in ovarian cancer facilitates tumor progression and resistance to immunotherapy. The function of MYB Proto-Oncogene Like 2 (MYBL2) in the tumor microenvironment remains largely unexplored.

Methods

A syngeneic intraovarian mouse model, flow cytometry analysis, and immunohistochemistry were used to explore the biological function of MYBL2 in tumor progression and immune escape. Molecular and biochemical strategies—namely RNA-sequencing, western blotting, quantitative reverse transcription–polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay, multiplex immunofluorescence, chromatic immunoprecipitation assay (CHIP) and luciferase assay—were used to reveal the mechanisms of MYBL2 in the OVC microenvironment.

Results

We found tumor derived MYBL2 indicated poor prognosis and selectively correlated with tumor associated macrophages (TAMs) in ovarian cancer. Mechanically, C-C motif chemokine ligand 2 (CCL2) transcriptionally activated by MYBL2 induced TAMs recruitment and M2-like polarization in vitro. Using a syngeneic intraovarian mouse model, we identified MYBL2 promoted tumor malignancyand increased tumor-infiltrating immunosuppressive macrophages. Cyclin-dependent kinase 2 (CDK2) was a known upstream kinase to phosphorylate MYBL2 and promote its transcriptional function. The upstream inhibitor of CDK2, CVT-313, reprogrammed the tumor microenvironment and reduced anti-PD-1 resistance.

Conclusions

The MYBL2/CCL2 axis contributing to TAMs recruitment and M2-like polarization is crucial to immune evasion and anti-PD-1 resistance in ovarian cancer, which is a potential target to enhance the efficacy of immunotherapy.
Association between total cholesterol and lumbar bone density in Chinese: a study of physical examination data from 2018 to 2023
Authors: Sun Yongbing , Qi Xin , Lin Xinbei , Zhou Yang , Lv Xue , Zhou Jing , Li Zhonglin , Wu Xiaoling , Zou Zhi , Li Yongli , Li Hao
Published: October 2023

Background

The impact of total cholesterol (TC) on lumbar bone mineral density (BMD) is a topic of interest. However, empirical evidence on this association from demographic surveys conducted in China is lacking. Therefore, this study aimed to examine the relationship between serum TC and lumbar BMD in a sample of 20,544 Chinese adults between the ages of 20 and 80 years over a period of 5 years, from February 2018 to February 2023. Thus, we investigated the effect of serum TC level on lumbar BMD and its relationship with bone reduction in a Chinese adult population.

Methods

This cross-sectional study used data obtained from the Department of Health Management at Henan Provincial People’s Hospital between February 2018 and February 2023. The aim of this study was to examine the correlation between serum TC and lumbar BMD in individuals of different sexes. The research methodology encompassed population description, analysis of stratification, single-factor and multiple-equation regression analyses, smooth curve fitting, and analysis of threshold and saturation effects. The R and EmpowerStats software packages were used for statistical analysis.

Results

After adjusting for confounding variables, a multiple linear regression model revealed a significant correlation between TC and lumbar BMD in men. In subgroup analysis, serum TC was found to have a positive association with lumbar BMD in men, specifically those aged 45 years or older, with a body mass index (BMI) ranging from 24 to 28 kg/m2. A U-shaped correlation arose between serum TC and lumbar BMD was detected in women of different ages and BMI, the inflection point was 4.27 mmol/L for women aged ≥ 45 years and 4.35 mmol/L for women with a BMI of ≥ 28 kg/m2.

Conclusion

In this study, Chinese adults aged 20–80 years displayed different effects of serum TC on lumbar BMD in sex-specific populations. Therefore, monitoring BMI and serum TC levels in women of different ages could prevent osteoporosis and osteopenia.

Trial registration

The research protocol was approved by the Ethics Committee of Beijing Jishuitan Hospital, in accordance with the Declaration of Helsinki guidelines (No. 2015-12-02). These data are part of the China Health Quantitative CT Big Data Research team, which has been registered at clinicaltrials.gov (code: NCT03699228).