bluuebunny/crossref_metadata_2025 huggingface dataset:
New ASH initiatives to improve patient care of the long-overlooked Sickle Cell Disease
Authors: Tubman Venée N , Mohandas Narla , Abrams Charles S.
Published: May 2023

Due to the unique biology of sickle cell disease, as well as the societal disadvantages and racial inequities suffered by these patients, individuals with sickle cell disease have not benefited from the same remarkable advances in care and therapeutics as other hematologic disorders. Life expectancy of individuals with sickle cell disease is shortened by approximately 20 years even with optimal clinical care, and infant mortality continues to be a major concern in low-income countries. As hematologists, we must do more. ASH and the ASH Research Collaborative have instituted a multi-pronged initiative to improve the lives of individuals living with this disease. Here we describe two components of this ASH initiative, the Consortium on Newborn Screening in Africa (CONSA) to improve early diagnosis of infants in low-resource countries, and the Sickle Cell Disease Clinical Trial Network to accelerate the development of more effective therapeutics and care for those with this disorder. The combination of sickle cell disease-focused initiatives, the ASH Research Collaborative, CONSA, and the Sickle Cell Clinical Trials Network, have enormous potential to dramatically alter the course of sickle cell disease worldwide. We believe that the timing is ripe to embark on these critical and worthwhile initiatives and improve the lives of individuals with this disease.
Genetic Mapping of the Root Mycobiota in Rice and its Role in Drought Tolerance
Authors: Andreo-Jimenez Beatriz , te Beest Dennis E. , Kruijer Willem , Vannier Nathan , Kadam Niteen N. , Melandri Giovanni , Jagadish S. V. Krishna , van der Linden Gerard , Ruyter-Spira Carolien , Vandenkoornhuyse Philippe , Bouwmeester Harro J.
Published: May 2023

Background

Rice is the second most produced crop worldwide, but is highly susceptible to drought. Micro-organisms can potentially alleviate the effects of drought. The aim of the present study was to unravel the genetic factors involved in the rice-microbe interaction, and whether genetics play a role in rice drought tolerance. For this purpose, the composition of the root mycobiota was characterized in 296 rice accessions (Oryza sativa L. subsp. indica) under control and drought conditions. Genome wide association mapping (GWAS) resulted in the identification of ten significant (LOD > 4) single nucleotide polymorphisms (SNPs) associated with six root-associated fungi: Ceratosphaeria spp., Cladosporium spp., Boudiera spp., Chaetomium spp., and with a few fungi from the Rhizophydiales order. Four SNPs associated with fungi-mediated drought tolerance were also found. Genes located around those SNPs, such as a DEFENSIN-LIKE (DEFL) protein, EXOCYST TETHERING COMPLEX (EXO70), RAPID ALKALINIZATION FACTOR-LIKE (RALFL) protein, peroxidase and xylosyltransferase, have been shown to be involved in pathogen defense, abiotic stress responses and cell wall remodeling processes. Our study shows that rice genetics affects the recruitment of fungi, and that some fungi affect yield under drought. We identified candidate target genes for breeding to improve rice-fungal interactions and hence drought tolerance.
Isolation and characterization of bacteriophages for combating multidrug-resistant Listeria monocytogenes from dairy cattle farms in conjugation with silver nanoparticles
Authors: Elsayed Mona M. , Elkenany Rasha M. , Zakari Amira I. , Badawy Basma M.
Published: May 2023

Background

This study aims to achieve biocontrol of multidrug-resistant Listeria monocytogenes in dairy cattle farms which poses a severe threat to our socio-economic balance and healthcare systems.

Methods

Naturally occurring phages from dairy cattle environments were isolated and characterized, and the antimicrobial effect of isolated L. monocytogenes phages (LMPs) against multidrug-resistant L. monocytogenes strains were assessed alone and in conjugation with silver nanoparticles (AgNPs).

Results

Six different phenotypic LMPs (LMP1–LMP6) were isolated from silage (n = 4; one by direct phage isolation and three by enrichment method) and manure (n = 2; both by enrichment method) from dairy cattle farms. The isolated phages were categorized into three different families by transmission electron microscopy (TEM): Siphoviridae (LMP1 and LMP5), Myoviridae (LMP2, LMP4, and LMP6), and Podoviridae (LMP3). The host range of the isolated LMPs was determined by the spot method using 22 multidrug-resistant L. monocytogenes strains. All 22 (100%) strains were susceptible to phage infection; 50% (3 out of 6) of the isolated phages showed narrow host ranges, while the other 50% showed moderate host ranges. We found that LMP3 (the phage with the shortest tail) had the ability to infect the widest range of L. monocytogenes strains. Eclipse and latent periods of LMP3 were 5 and 45 min, respectively. The burst size of LMP3 was 25 PFU per infected cell. LMP3 was stable with wide range of pH and temperature. In addition, time-kill curves of LMP3 alone at MOI of 10, 1 and 0.1, AgNPs alone, and LMP3 in combination with AgNPs against the most phage-resistant L. monocytogenes strain (ERIC A) were constructed. Among the five treatments, AgNPs alone had the lowest inhibition activity compared to LMP3 at a multiplicity of infection (MOI) of 0.1, 1, and 10. LMP3 at MOI of 0.1 in conjugation with AgNPs (10 µg/mL) exhibited complete inhibition activity after just 2 h, and the inhibition activity lasted for 24 h treatment. In contrast, the inhibition activity of AgNPs alone and phages alone, even at MOI of 10, stopped. Therefore, the combination of LMP3 and AgNPs enhanced the antimicrobial action and its stability and reduced the required concentrations of LMP3 and AgNPs, which would minimize the development of future resistance.

Conclusions

The results suggested that the combination of LMP3 and AgNPs could be used as a powerful and ecofriendly antibacterial agent in the dairy cattle farm environment to overcome multidrug-resistant L. monocytogenes.
High correlation of hepatic shear wave velocity with esophageal varices complication rate in patients with chronic liver diseases
Authors: Namikawa Shouichi , Nosaka Takuto , Matsuda Hidetaka , Akazawa Yu , Takahashi Kazuto , Naito Tatsushi , Ohtani Masahiro , Nakamoto Yasunari
Published: May 2023

Background

Histological evaluation by liver biopsy is considered the gold standard for assessing liver disease; however, it is highly invasive. Non-invasive liver stiffness measurement by shear wave elastography (SWE) is effective for evaluating the hepatic fibrosis stage and related diseases. In this study, we investigated the correlations of liver stiffness with hepatic inflammation/fibrosis, functional hepatic reserve, and related diseases in patients with chronic liver disease (CLD).

Methods

Shear wave velocity (Vs) values were measured using point SWE in 71 patients with liver disease from 2017 to 2019. Liver biopsy specimens and serum biomarkers were collected at the same time, and splenic volume was measured using computed tomography images with the software Ziostation2. Esophageal varices (EV) were evaluated by upper gastrointestinal endoscopy.

Results

Among CLD-related function and complications, Vs values were highly correlated with liver fibrosis and EV complication rates. The median Vs values for liver fibrosis grades F0, F1, F2, F3, and F4 were 1.18, 1.34, 1.39, 1.80, and 2.12 m/s, respectively. Comparison of receiver operating characteristic (ROC) curves to predict cirrhosis showed that area under the ROC (AUROC) curve for Vs values was 0.902, which was not significantly different from the AUROCs for the FIB-4 index, platelet count, hyaluronic acid, or type IV collagen 7S, while it was significantly different from the AUROC for mac-2 binding protein glycosylation isomer (M2BPGi) (P < 0.01). Comparison of ROC curves to predict EV showed that the AUROC for Vs values was 0.901, which was significantly higher than the AUROCs for FIB-4 index (P < 0.05), platelet count (P < 0.05), M2BPGi (P < 0.01), hyaluronic acid (P < 0.05), and splenic volume (P < 0.05). In patients with advanced liver fibrosis (F3 + F4), there was no difference in blood markers and splenic volume, while Vs value was significantly higher in patients with EV (P < 0.01).

Conclusions

Hepatic shear wave velocity was highly correlated with EV complication rates in chronic liver diseases as compared to blood markers and splenic volume. In advanced CLD patients, Vs values of SWE are suggested to be effective in predicting the appearance of EV noninvasively.
The impact of multi-drug resistant Pseudomonas aeruginosa infections on acute pancreatitis patients
Authors: Wu Di , Lu Wenjun , Huang Yilin , Qin Ge , liu Huanmiao , Xiao Jie , Peng Jie
Published: May 2023

Introduction

Acute pancreatitis (AP) accounts for a high proportion of digestive diseases worldwide and has a high risk of infection. Pseudomonas aeruginosa, a common pathogen of hospital infections, has been observed to increase the resistance rate to several antibiotics, causing difficulties in treatments. Our study aims to investigate the impact of the multi-drug resistant Pseudomonas aeruginosa (MDR-PA) infections on AP patients.

Methods

At two Chinese tertiary referral centers for AP patients infected with MDR-PA, a retrospective case-control study with a 1:2 case-control ratio was performed. Comparisons were preformed between with/without MDR-PA infections and different drug-resistance of MDR-PA infections patients, respectively. Independent risk factors of overall mortality were assessed via univariate and multivariate binary logistic regression analyses, and the distribution and antibiotic resistant rates of strains were described.

Results

Mortality in AP patients with MDR-PA infections was significantly higher than in those without MDR-PA infections (7 (30.4%) vs. 4 (8.7%), P = 0.048). The rate of prophylactic use of carbapenem for 3 days (0 vs. 50%, P = 0.019) and the incidence rate of multiple organ failure (MOF) (0 vs. 57.1%, P = 0.018) were remarkably higher in the carbapenem-resistant Pseudomonas aeruginosa group compared with the carbapenem-sensitive Pseudomonas aeruginosa group. In the multivariate analysis, the severe categories of AP (OR = 13.624, 95% CIs = 1.567–118.491, P = 0.018) and MDR-PA infections (OR = 4.788, 95% CIs = 1.107–20.709, P = 0.036) were independent risk factors for mortality. The resistance rates of MDR-PA strains were low for amikacin (7.4%), tobramycin (3.7%), and gentamicin (18.5%). The resistance rates of MDR-PA strains to imipenem and meropenem were up to, 51.9% and 55.6%, respectively.

Conclusion

In AP patients, severe categories of AP and MDR-PA infections were both independent risk factors for mortality. Inappropriate use of carbapenem antibiotics and MOF were related to carbapenem-resistant Pseudomonas aeruginosa infections. Amikacin, tobramycin, and gentamicin are recommended for the treatment of AP patients with MDR-PA infections.
Study protocol of an open-label, single arm phase II trial investigating the efficacy and safety of Trifluridine/Tipiracil combined with irinotecan as a second line therapy in patients with cholangiocarcinoma (TRITICC)
Authors: Kehmann Linde , Berres Marie-Luise , Gonzalez-Carmona Maria , Modest Dominik P. , Mohr Raphael , Wree Alexander , Venerito Marino , Strassburg Christian , Keitel Verena , Trautwein Christian , Luedde Tom , Roderburg Christoph
Published: May 2023

Background

The prognosis of patients with advanced biliary tract cancer (BTC) who have progressed on gemcitabine plus cisplatin is dismal. Trifluridine/tipiracil (FTD/TPI) and irinotecan have proven efficacy in different gastrointestinal malignancies. We therefore hypothesized that this combination might improve the therapeutic outcome in patients with BTC after failure of first line treatment.

Methods

TRITICC is an interventional, prospective, open-label, non-randomised, exploratory, multicentre, single-arm phase IIA clinical trial done in 6 sites with expertise in managing biliary tract cancer across Germany. A total of 28 adult patients (aged ≥ 18 years) with histologically verified locally advanced or metastatic biliary tract cancer (including cholangiocarcinoma and gallbladder or ampullary carcinoma) with documented radiological disease progression to first-line gemcitabine based chemotherapy will be included to receive a combination of FTD/TPI plus irinotecan according to previously published protocols. Study treatment will be continued until disease progression according to RECIST 1.1 criteria or occurrence of unacceptable toxicity. The effect of FTD/TPI plus irinotecan on progression-free survival will be analyzed as primary endpoint. Safety (according to NCI-CTCAE), response rates and overall survival are secondary endpoints. In addition, a comprehensive translational research program is part of the study and might provide findings about predictive markers with regard to response, survival periods and resistance to treatment.

Discussion

The aim of TRITICC is to evaluate the safety and efficacy of FTD/TPI plus irinotecan in patients with biliary tract cancer refractory to previous Gemcitabine based treatment.

Trial registration

EudraCT 2018–002936-26; NCT04059562
Evaluation and correlation analysis of ocular surface disorders and quality of life in autoimmune rheumatic diseases: a cross-sectional study
Authors: Ren Yuerong , Tian Jing , Shi Wen , Feng Jianing , Liu Yingyi , Kang Huanmin , Chen Baihua , He Yan
Published: May 2023

Objective

This cross-sectional study aimed to reveal the association between ocular surface disorders and psychological, physiological situations among autoimmune rheumatic patients.

Methods

Ninety autoimmune rheumatic patients (180 eyes) hospitalized in the Department of Rheumatology, The Second Xiangya Hospital, Central South University and 30 controls (60 eyes) were enrolled in the study. All participants were assessed for ocular surface disorders including dry eye disease (DED) by the Ocular Surface Disease Index (OSDI) for symptoms evaluation, and slim lamp examinations for tear break-up time (TBUT), meibomian gland secretion, symblepharon and corneal clarity, Schirmer I test, corneal fluorescein staining (CFS), lid-parallel conjunctival folds (LIPCOF). Systematic conditions were evaluated using the Short Form 36-Health Survey (SF-36) for health-related quality of life, Hospital Anxiety and Depression Scale (HADS) for anxiety and depression, Health Assessment Questionnaire-Disability Index (HAQ-DI) for difficulties in activities of daily living, and Pittsburgh Sleep Quality Index (PSQI) for sleep quality. Pearson and spearman’s analysis were conducted to examine the relationship between systematic conditions and ocular surface conditions.

Results

The analyses were controlled for age and sex. 52.22% of eyes (94 in 180) of autoimmune rheumatic patients and 21.67% of eyes (13 in 60) of controls were diagnosed with DED. The autoimmune rheumatic patients showed significant higher OSDI score, fewer basal tear secretion, more severe CFS and conjunctivochalasis than controls. There were no statistically significant differences in TBUT, meibomian gland secretion, symblepharon, and corneal clarity between the two groups. For systematic conditions, autoimmune rheumatic patients had significantly lower SF-36 scores, higher anxiety scores, and HAQ-DI scores than controls. No statistically significant differences were detected in depression scores and PSQI between the two groups. Among autoimmune rheumatic patients, OSDI scores were moderately correlated with quality of life, anxiety, depression and sleep quality.

Conclusion

Factors including quality of life, anxiety, depression, and sleep quality are associated with ocular surface conditions, especially DED symptoms. Management of systemic conditions and psychotherapy should also be considered as part of the treatment among autoimmune rheumatic patients.
New-onset stroke on the risk of hip fracture: the Kailuan cohort study in China
Authors: Zhang Nan , Guo Lu , Yu Yaohui , Chen Shuohua , Gao Lishu , Hou Xiaoli , Tian Faming , Wu Shouling
Published: May 2023

Purpose

Stroke is a documented risk factor for hip fracture(HF). However, no data is currently available on this issue in mainland China, we therefore assessed the risk of hip fracture after new-onset stroke using a cohort study.

Methods

This study included 165,670 participants without a history of stroke at baseline from the Kailuan study. All participants were followed biennially until December 31, 2021. During follow-up, a total of 8,496 new-onset stroke cases were identified. For each case subject, four control subjects was randomly selected, matched for age (± 1 years) and sex. The final analysis comprised 42,455 pair-matched cases and controls. A multivariate Cox proportional hazard regression model was used to estimate the effect of new-onset stroke on the risk of hip fracture.

Results

During an average follow-up of 8.87 (3.94) years, a total of 231 hip fracture cases occurred, 78 cases in the stroke group and 153 cases in the control group, with incidence rates of 1.12 and 0.50 per 1000 person-years, respectively. The cumulative incidence of the stroke group was higher than that of the controls (P < 0.01). The adjusted hazard ratio (95% confidence interval) of hip fractures in the stroke group was 2.35 (1.77 to 3.12) (P < 0.001) to controls. After stratifying by gender, age, and body mass index, the higher risk was revealed in female (HR 3.10, 95 CI: 2.18 to 6.14, P < 0.001), age < 60 years old (HR 4.12, 95% CI: 2.18 to 7.78, P < 0.001), and non-obesity (BMI<28 kg/m2) (HR 1.74, 95% CI:1.31 to 2.31, P < 0.001) subgroup.

Conclusions

Stroke significantly increases the risk of hip fracture, strategy for protecting stroke patients from falls and hip fractures should be emphasized in poststroke long-term management, particularly the female, age < 60 years old, and non-obese patients.
Biomechanical effect of endplate defects on the intermediate vertebral bone in consecutive two-level anterior cervical discectomy and fusion: a finite element analysis
Authors: Zhang Jiarui , Chen Wenzhao , Weng Rui , Liang De , Jiang Xiaobing , Lin Hongheng
Published: May 2023

Background

Intermediate vertebral collapse is a newly discovered complication of consecutive two-level anterior cervical discectomy and fusion (ACDF). There have been no analytical studies related to the effects of endplate defects on the biomechanics of the intermediate vertebral bone after ACDF. This study aimed to compare the effects of endplate defects on the intermediate vertebral bone biomechanics in the zero-profile (ZP) and cage-and-plate (CP) methods of consecutive 2-level ACDF and to determine whether collapse of the intermediate vertebra is more likely to occur using ZP.

Methods

A three-dimensional finite element (FE) model of the intact cervical spine (C2–T1) was constructed and validated. The intact FE model was then modified to build ACDF models and imitate the situation of endplate injury, establishing two groups of models (ZP, IM-ZP and CP, IM-ZP). We simulated cervical motion, such as flexion, extension, lateral bending and axial rotation, and compared the range of motion (ROM), upper and lower endplate stress, fusion fixation device stress, C5 vertebral body stress, intervertebral disc internal pressure (intradiscal pressure, or IDP) and the ROM of adjacent segments in the models.

Results

There was no significant difference between the IM-CP model and the CP model in the ROM of the surgical segment, upper and lower endplate stress, fusion fixation device stress, C5 vertebral body stress, IDP, or ROM of the adjacent segments. Compared with the CP model, the endplate stress of the ZP model is significantly higher in the flexion, extension, lateral bending and axial rotation conditions. Compared with the ZP model, endplate stress, screw stress, C5 vertebral stress and IDP in IM-ZP were significantly increased under flexion, extension, lateral bending and axial rotation conditions.

Conclusions

Compared to consecutive 2-level ACDF using CP, collapse of the intermediate vertebra is more likely to occur using ZP due to its mechanical characteristics. Intraoperative endplate defects of the anterior lower margin of the middle vertebra are a risk factor leading to collapse of the middle vertebra after consecutive 2-level ACDF using ZP.
Computerized dynamic occlusal analysis and its correlation with static characters in post-orthodontic patients using the T-Scan system and the ABO objective grading system
Authors: Wang Menglin , Liu Le , Ma Xihua , Jin Xiang , Zhang Zhenbao , Jia Xiangmin , Fan Jiadong , Tang Haoning , Li Yanfeng
Published: May 2023

Objectives

This study was conducted to detect the overall performance of both static and dynamic occlusion in post-orthodontic patients using quantified methods, and to ascertain the correlation between the two states of occlusion.

Materials and methods

A total of 112 consecutive patients evaluated by ABO-OGS were included in this study. Based on the pre-treatment Angle’s classification of the malocclusion, samples were divided into four groups. After removing orthodontic appliances, each patients underwent the American Board of Orthodontic objective grading system (ABO-OGS) and T-Scan evaluations. All the scores were compared within these groups. Statistical evaluation included reliability tests, multivariate ANOVA, and correlation analyses (p < 0.05 was considered significant).

Results

The mean ABO-OGS score was satisfactory and did not differ by Angle classifications. The indices making substantial contributions to ABO-OGS were occlusal contacts, occlusal relationships, overjet, and alignment. Disocclusion time in post-orthodontic patients was longer than normal. Occlusion time, disocclusion time, and force distribution during dynamic motions were considerably influenced by static ABO-OGS measurements, especially occlusal contacts, buccolingual inclination, and alignment.

Conclusion

Post-orthodontic cases that passed the static evaluation of clinicians and ABO-OGS may nevertheless be left with dental casts interference in dynamic motions. Both static and dynamic occlusion should be extensively evaluated before ending orthodontic treatment. Further research is needed on dynamic occlusal guidelines and standards.
Survival analysis of implants after surgical treatment of peri-implantitis based on bone loss severity and surgical technique: a retrospective study
Authors: Hwang Sooshin , Lee Hee-min , Yun Pil-Young , Kim Young-Kyun
Published: May 2023

Background

Few trials have compared the results of surgical treatment for peri-implantitis based on severity of peri-implantitis and surgical method. This study investigated the survival rate of implants based on type of surgical method used and initial severity of peri-implantitis. Classification of severity was determined based on bone loss rate relative to fixture length.

Methods

Medical records of patients who underwent peri-implantitis surgery from July 2003 to April 2021 were identified. Classification of peri-implantitis was divided into 3 groups (stage 1: bone loss < 25% (of fixture length), stage 2: 25% < bone loss < 50%, stage 3: bone loss > 50%) and performance of resective or regenerative surgery was investigated. Kaplan-Meier survival curves and Cox hazards proportional models were used to analyze the cumulative survival rate of implants. Median survival time, predicted mean survival time, hazard ratio (HR), and 95% confidence interval (CI) were calculated.

Results

Based on Kaplan-Meier analysis, 89 patients and 227 implants were included, and total median postoperative survival duration was 8.96 years. Cumulative survival rates for stage 1, 2, and 3 were 70.7%, 48.9%, and 21.3%, respectively. The mean survival time for implants in stage 1, 2, and 3 was 9.95 years, 7.96 years, and 5.67 years, respectively, with statistically significant difference (log-rank p-value < 0.001). HRs for stage 2 and stage 3 were 2.25 and 4.59, respectively, with stage 1 as reference. Significant difference was not found in survival time between resective and regenerative surgery groups in any peri-implantitis stage.

Conclusions

The initial bone loss rate relative to the fixture length significantly correlated with the outcome after peri-implantitis surgery, demonstrating a notable difference in the long-term survival rate. Difference was not found between resective surgery and regenerative surgery in implant survival time. Bone loss rate could be utilized as a reliable diagnostic tool for evaluating prognosis after surgical treatment, regardless of surgical method used.

Trial registration

Retrospectively registered. (KCT0008225)
Pre-dental treatment screening in Indonesia during the COVID-19 pandemic: a questionnaire survey of dental practitioners
Authors: Widyarman Armelia Sari , Roeslan Moehamad Orliando , Dewanto Iwan
Published: May 2023

Background

Dental practitioners have a high risk of contracting COVID-19 during the treatment of patients because of exposure to airborne droplets. However, the application of pre-procedure treatment screening in dental practices in Indonesia varied during the pandemic. The purpose of this study was to investigate the use of updated pre-procedure dental treatment protocols and procedures among dental practitioners in Indonesia.

Methods

This study consisted of dentists registered as members of the Indonesian Dental Association who attended the Indonesian Dental Association webinar series in 2021. All the participants completed a questionnaire survey. The participants, who were from various regions in Indonesia, were granted password-protected access to a URL hosting the questionnaire. The questionnaire collected demographic information and contained questions on adherence to updated protocols and patient screening procedures, to which the respondents answered “Yes” or “No”. For the analysis, the participants were divided into three groups based on the type of facility where they were employed: public (government) hospitals, private hospitals, or university hospitals (dental schools). A chi-square test was used to investigate the association between professional background and the implementation of updated protocols, including pre-procedure dental treatment screening. A value of P < 0.05 was considered statistically significant.

Results

The age range of the participants was 20 − 60 years. The participants worked in facilities in 32 provinces in Indonesia. In total, there were 5,323 participants (males: n = 829; females: n = 4,494). In terms of professional backgrounds, 2,171, 2,867, and 285 participants were employed in government hospitals, private hospitals, and dental faculties, respectively. Among 5,232 participants who implemented updated COVID-19 prevention protocols, 5,053 (98%) participants performed pre-surgery procedures Among 151 participants who did not implement updated COVID-19 prevention protocols, 133 (88%) individuals carried out pre-rinse procedures.

Conclusions

Almost all the dental practitioners employed in government hospitals, private hospitals, and dental faculties in Indonesia performed pre-surgery patient screening procedures. There was an agreement between the dental professionals in all three settings on the need for COVID-19 pre-treatment screening procedures in dental practices during the COVID-19 pandemic.
Effects of probiotics on pancreatic inflammation and intestinal integrity in mice with acute pancreatitis
Authors: Werawatganon Duangporn , Vivatvakin Sarocha , Somanawat Kanjana , Tumwasorn Somying , Klaikeaw Naruemon , Siriviriyakul Prasong , Chayanupatkul Maneerat
Published: May 2023

Background

Severe acute pancreatitis is a potentially life-threatening disease. Despite being a common disorder, acute pancreatitis lacks a specific treatment. The present study aimed to examine the effects of probiotics on pancreatic inflammation and intestinal integrity in mice with acute pancreatitis.

Methods

Male ICR mice were randomly divided into 4 groups (n = 6 per group). The control group received two intraperitoneal (i.p.) injections of normal saline as a vehicle control. The acute pancreatitis (AP) group received two i.p. injections of L-arginine 450 mg/100 g body weight. AP plus probiotics groups received L-arginine to induce acute pancreatitis as above. In the single-strain and mixed-strain groups, mice received 1 mL of Lactobacillus plantarum B7 1 × 108 CFU/mL and 1 mL of Lactobacillus rhamnosus L34 1 × 108 CFU/mL and Lactobacillus paracasei B13 1 × 108 CFU/mL by oral gavage, respectively for 6 days starting 3 days prior to the AP induction. All mice were sacrificed 72 h after L-arginine injection. Pancreatic tissue was obtained for histological evaluation and immunohistochemical studies for myeloperoxidase, whereas ileal tissue was used for immunohistochemical studies for occludin, and claudin-1. Blood samples were collected for amylase analysis.

Results

Serum amylase levels and pancreatic myeloperoxidase levels in the AP group were significantly higher than in controls and significantly decreased in probiotic groups compared with the AP group. Ileal occludin and claudin-1 levels were significantly lower in the AP group than in controls. Ileal occludin levels significantly increased, whereas ileal claudin-1 levels did not significantly change in both probiotic groups as compared with the AP group. The pancreatic histopathology showed significantly higher degree of inflammation, edema, and fat necrosis in the AP group, and these changes improved in mixed-strained probiotic groups.

Conclusions

Probiotics, particularly the mixed-strain ones, attenuated AP via the reduction of inflammation and the maintenance of intestinal integrity.
The effects of developmental model of peer observation on the virtual teaching quality of basic medical sciences faculty
Authors: Doroh Mohammad Habibi , Farajpour Arezou , Amirmajdi Elham Mokhtari
Published: May 2023

Background

After the Corona pandemic, medical education has shifted to virtual education, but there has been limited time and possibilities for empowering faculty for this purpose. Therefore, it seems necessary to evaluate the quality of the provided training and provide feedback to the faculty in order to improve the quality of training. The purpose of this study was to investigate the effect of teacher formative evaluation by peer observation method on the quality of virtual teaching of basic medical sciences faculty.

Methods

In this study, seven trained faculty members observed and based on a checklist evaluated the quality of 2 virtual sessions taught by each faculty of basic medical sciences, and provided them feedback; after at least 2 weeks, their Virtual teachings were again observed and evaluated. The results before and after providing feedback were compared through SPSS software.

Results

After intervention, significant improvements were observed in the average scores of “overall virtual performance”, “virtual classroom management” and “content quality”. Specifically, there was a significant increase in the average score of “overall virtual performance” and “virtual class management” among female faculty, and the average score of “overall virtual performance” among permanently employed faculty members with more than 5 years of teaching experience, before and after intervention (p < 0.05).

Conclusion

Virtual and online education can be a suitable platform for the implementation of formative and developmental model of peer observation of faculty; and should be considered as an opportunity to empower and improve the quality of the faculty’ performance in virtual education.
The impact of pandemic disruptions on clinical skills learning for pre-clinical medical students: implications for future educational designs
Authors: Saad Shannon , Richmond Cassandra , King Dane , Jones Caelyn , Malau-Aduli Bunmi
Published: May 2023

Background

Pandemic disruptions to medical education worldwide resulted in rapid adaptations to clinical skills learning. These adaptations included moving most teaching to the online environment, decreasing the accepted “hands-on” methods of teaching and learning. While studies have shown significant impacts on student confidence in skills acquisition, there is a paucity of assessment outcome studies which would contribute a valuable perspective on whether measurable deficits were incurred. Here, a preclinical (Year 2) cohort was investigated for clinical skills learning impacts that could influence their transition to hospital-based placements.

Methods

A sequential mixed methods approach was used on the Year 2 Medicine cohort, including: focus group discussions with thematic analysis; a survey derived from the themes observed; and a cohort comparison of the clinical skills examination results of the disrupted Year 2 cohort, compared to pre-pandemic cohorts.

Results

Students reported experiencing benefits and disadvantages of the shift to online learning, including a decrease in confidence in their skills acquisition. End of year summative clinical assessments showed non-inferior outcomes when compared to previous cohorts for the majority of clinical skills. However, for procedural skills (venepuncture) the disrupted cohort had significantly lower scores compared to a pre-pandemic cohort.

Conclusions

Rapid innovation during the COVID-19 pandemic provided the opportunity to compare online asynchronous hybrid clinical skills learning with the usual practice of face-to-face synchronous experiential learning. In this study, students’ reported perceptions and assessment performance data indicate that careful selection of skills suitable for online teaching, supported by timetabled “hands-on” sessions and ample practice opportunities, is likely to provide non-inferior outcomes for clinical skills learning in students about to transition to clinical placements. The findings can be used to inform clinical skills curriculum designs that incorporate the virtual environment, and assist with future-proofing skills teaching in the case of further catastrophic disruptions.
Medical school origins of award-winning surgeons; analysis of a complete national dataset
Authors: Steele S. , Andrade G. , Sambandan N.
Published: May 2023

Background

Britain attracts doctors from all over the world to work in the National Health Service. Elucidating the educational backgrounds of award-winning doctors working in the country is potentially an important medical education issue and merit award audit. Using the British clinical merit award schemes as outcome measures, we identify medical school origins of award-winning doctors who have been identified as having achieved national or international prominence.

Methods

The Clinical Excellence Awards/Distinction Awards schemes select doctors in Britain who are classified as high achievers, with categories for national prominence and above. We used this outcome measure in a quantitative observational analysis of the 2019 dataset of all 901 award-winning doctors. Pearson's Chi-Square test was used where appropriate.

Results

Seven medical schools (London university medical schools, Glasgow, Edinburgh, Aberdeen, Oxford, Cambridge and Manchester) accounted for 52.7% of the surgical award-winning doctors in the 2019 round, despite the dataset representing 85 medical schools. Surgeons with the lower grade national awards came from a more diverse educational background of 43 medical schools. International medical graduates accounted for 16.1% of the award-winning surgeons and 9.8% of the award-winning non-surgeons. 87.1% of the surgical award-winners were from European medical schools, whereas 93.2% of the non-surgical award-winners were from European medical schools.

Conclusions

The majority of the award-winning surgeons originated from only seven, overrepresented, medical schools. A greater diversity of medical school origin existed for the lowest grade national merit awards. These comprised 43 medical schools and indicated greater globalization effects in this category. International medical graduates contributed substantially to these award holders; surgical award-winners were more likely to be international medical graduates (16.1%) than non-surgical award-winners (9.8%). This study not only indicates educational centres associated with the production of award-winners but also provides students with a roadmap for rational decision making when selecting medical schools.
Extracellular arginine availability modulates eIF2α O-GlcNAcylation and heme oxygenase 1 translation for cellular homeostasis
Authors: Hung Yu-Wen , Ouyang Ching , Ping Xiaoli , Qi Yue , Wang Yi-Chang , Kung Hsing-Jien , Ann David K.
Published: May 2023

Background

Nutrient limitations often lead to metabolic stress during cancer initiation and progression. To combat this stress, the enzyme heme oxygenase 1 (HMOX1, commonly known as HO-1) is thought to play a key role as an antioxidant. However, there is a discrepancy between the level of HO-1 mRNA and its protein, particularly in cells under stress. O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). The mechanism by which eIF2α O-GlcNAcylation regulates translation of HO-1 during extracellular arginine shortage (ArgS) remains unclear.

Methods

We used mass spectrometry to study the relationship between O-GlcNAcylation and Arg availability in breast cancer BT-549 cells. We validated eIF2α O-GlcNAcylation through site-specific mutagenesis and azido sugar N-azidoacetylglucosamine-tetraacylated labeling. We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions.

Results

Our research identified eIF2α, eIF2β, and eIF2γ, as key O-GlcNAcylation targets in the absence of Arg. We found that O-GlcNAcylation of eIF2α plays a crucial role in regulating antioxidant defense by suppressing the translation of the enzyme HO-1 during Arg limitation. Our study showed that O-GlcNAcylation of eIF2α at specific sites suppresses HO-1 translation despite high levels of HMOX1 transcription. We also found that eliminating eIF2α O-GlcNAcylation through site-specific mutagenesis improves cell recovery, migration, and reduces ROS accumulation by restoring HO-1 translation. However, the level of the metabolic stress effector ATF4 is not affected by eIF2α O-GlcNAcylation under these conditions.

Conclusions

Overall, this study provides new insights into how ArgS fine-tunes the control of translation initiation and antioxidant defense through eIF2α O-GlcNAcylation, which has potential biological and clinical implications.
Evolocumab attenuate pericoronary adipose tissue density via reduction of lipoprotein(a) in type 2 diabetes mellitus: a serial follow-up CCTA study
Authors: Yu Meng-Meng , Zhao Xin , Chen Yin-Yin , Tao Xin-Wei , Ge Jun-Bo , Jin Hang , Zeng Meng-Su
Published: May 2023

Background

Pericoronary adipose tissue (PCAT) density is a biomarker of vessel inflammation, which is supposed to be increased in patients with type 2 diabetes mellitus (T2DM). However, whether the coronary inflammation revealed by this novel index could be alleviated after evolocumab treatment in T2DM remains unknown.

Methods

From January 2020 to December 2022, consecutive T2DM patients with low-density lipoprotein cholesterol ≥ 70 mg/dL on maximally tolerated statin and taking evolocumab were prospectively included. In addition, patients with T2DM who were taking statin alone were recruited as control group. The eligible patients underwent baseline and follow-up coronary CT angiography with an interval of 48-week. To render patients with evolocumab as comparable to those controls, a propensity-score matching design was used to select the matched pairs with a 1:1 ratio. Obstructive lesion was defined as the extent of coronary artery stenosis ≥ 50%; the numbers inside the brackets were interquartile ranges.

Results

A total of 170 T2DM patients with stable chest pain were included [(mean age 64 ± 10.6 [range 40–85] years; 131 men). Among those patients, 85 were in evolocumab group and 85 were in control group. During follow-up, low-density lipoprotein cholesterol (LDL-C) level (2.02 [1.26, 2.78] vs. 3.34 [2.53, 4.14], p < 0.001), and lipoprotein(a) (12.1 [5.6, 21.8] vs. 18.9 [13.2, 27.2], p = 0.002) were reduced after evolocumab treatment. The prevalence of obstructive lesions and high-risk plaque features were significantly decreased (p < 0.05 for all). Furthermore, the calcified plaque volume were significantly increased (188.3 [115.7, 361.0] vs. 129.3 [59.5, 238.3], p = 0.015), while the noncalcified plaque volume and necrotic volume were diminished (107.5 [40.6, 180.6] vs. 125.0 [65.3, 269.7], p = 0.038; 0 [0, 4.7] vs. 0 [0, 13.4], p < 0.001, respectively). In addition, PCAT density of right coronary artery was significantly attenuated in evolocumab group (− 85.0 [− 89.0, − 82.0] vs. − 79.0 [− 83.5, − 74.0], p < 0.001). The change in the calcified plaque volume inversely correlated with achieved LDL-C level (r =  − 0.31, p < 0.001) and lipoprotein(a) level (r =  − 0.33, p < 0.001). Both the changes of noncalcified plaque volume and necrotic volume were positively correlated with achieved LDL-C level and Lp(a) (p < 0.001 for all). However, the change of PCATRCA density only positively correlated with achieved lipoprotein(a) level (r = 0.51, p < 0.001). Causal mediation analysis revealed Lp(a) level mediated 69.8% (p < 0.001) for the relationship between evolocumab and changes of PCATRCA.

Conclusions

In patients with T2DM, evolocumab is an effective therapy to decrease noncalcified plaque volume necrotic volume, and increase calcified plaque volume. Furthermore, evolocumab could attenuate PCAT density, at least in part, via the reduction of lipoprotein(a).
Electromagnetic fields ameliorate hepatic lipid accumulation and oxidative stress: potential role of CaMKKβ/AMPK/SREBP-1c and Nrf2 pathways
Authors: Zhai Mingming , Zhang Chenxu , Cui Jinxiu , Liu Juan , Li Yuanzhe , Xie Kangning , Luo Erping , Tang Chi
Published: May 2023

Background

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, and is related to disturbed lipid metabolism and redox homeostasis. However, a definitive drug treatment has not been approved for this disease. Studies have found that electromagnetic fields (EMF) can ameliorate hepatic steatosis and oxidative stress. Nevertheless, the mechanism remains unclear.

Methods

NAFLD models were established by feeding mice a high-fat diet. Simultaneously, EMF exposure is performed. The effects of the EMF on hepatic lipid deposition and oxidative stress were investigated. Additionally, the AMPK and Nrf2 pathways were analysed to confirm whether they were activated by the EMF.

Results

Exposure to EMF decreased the body weight, liver weight and serum triglyceride (TG) levels and restrained the excessive hepatic lipid accumulation caused by feeding the HFD. The EMF boosted CaMKKβ protein expression, activated AMPK phosphorylation and suppressed mature SREBP-1c protein expression. Meanwhile, the activity of GSH-Px was enhanced following an increase in nuclear Nrf2 protein expression by PEMF. However, no change was observed in the activities of SOD and CAT. Consequently, EMF reduced hepatic reactive oxygen species (ROS) and MDA levels, which means that EMF relieved liver damage caused by oxidative stress in HFD-fed mice.

Conclusions

EMF may activate the CaMKKβ/AMPK/SREBP-1c and Nrf2 pathways to control hepatic lipid deposition and oxidative stress. This investigation indicates that EMF may be a novel therapeutic method for NAFLD.
Efficacy and safety of particle therapy for inoperable stage II-III non-small cell lung cancer: a systematic review and meta-analysis
Authors: Chen Yanliang , Luo Hongtao , Liu Ruifeng , Tan Mingyu , Wang Qian , Wu Xun , Du Tianqi , Liu Zhiqiang , Sun Shilong , Zhang Qiuning , Wang Xiaohu
Published: May 2023

Background and purpose

Particle therapy, mainly including carbon-ion radiotherapy (CIRT) and proton beam therapy (PBT), has dose distribution advantages compared to photon radiotherapy. It has been widely reported as a promising treatment method for early non-small cell lung cancer (NSCLC). However, its application in locally advanced non-small cell lung cancer (LA-NSCLC) is relatively rare, and its efficacy and safety are inconclusive. This study aimed to provide systematic evidence for evaluating the efficacy and safety of particle therapy for inoperable LA-NSCLC.

Methods

To retrieve published literature, a systematic search was conducted in PubMed, Web of Science, Embase, and Cochrane Library until September 4, 2022. The primary endpoints were local control (LC) rate, overall survival (OS) rate, and progression-free survival (PFS) rate at 2 and 5 years. The secondary endpoint was treatment-related toxicity. The pooled clinical outcomes and 95% confidence intervals (CIs) were calculated by using STATA 15.1.

Results

Nineteen eligible studies with a total sample size of 851 patients were included. The pooled data demonstrated that the OS, PFS, and LC rates at 2 years of LA-NSCLC treated by particle therapy were 61.3% (95% CI = 54.7-68.7%), 37.9% (95% CI = 33.8-42.6%) and 82.2% (95% CI = 78.7-85.9%), respectively. The pooled 5-year OS, PFS, and LC rates were 41.3% (95% CI = 27.1-63.1%), 25.3% (95% CI = 16.3-39.4%), and 61.5% (95% CI = 50.7-74.6%), respectively. Subgroup analysis stratified by treatment type showed that the concurrent chemoradiotherapy (CCRT, PBT combined with concurrent chemotherapy) group had better survival benefits than the PBT and CIRT groups. The incidence rates of grade 3/4 esophagitis, dermatitis, and pneumonia in LA-NSCLC patients after particle therapy were 2.6% (95% CI = 0.4-6.0%), 2.6% (95% CI = 0.5-5.7%) and 3.4% (95% CI = 1.4-6.0%), respectively.

Conclusions

Particle therapy demonstrated promising efficacy and acceptable toxicity in LA-NSCLC patients.
Fibroblast growth factor 21 attenuates ventilator-induced lung injury by inhibiting the NLRP3/caspase-1/GSDMD pyroptotic pathway
Authors: Ding Peng , Yang Rui , Li Cheng , Fu Hai-Long , Ren Guang-Li , Wang Pei , Zheng Dong-Yu , Chen Wei , Yang Li-Ye , Mao Yan-Fei , Yuan Hong-Bin , Li Yong-Hua
Published: May 2023

Background

Ventilator-induced lung injury (VILI) is caused by overdistension of the alveoli by the repetitive recruitment and derecruitment of alveolar units. This study aims to investigate the potential role and mechanism of fibroblast growth factor 21 (FGF21), a metabolic regulator secreted by the liver, in VILI development.

Methods

Serum FGF21 concentrations were determined in patients undergoing mechanical ventilation during general anesthesia and in a mouse VILI model. Lung injury was compared between FGF21-knockout (KO) mice and wild-type (WT) mice. Recombinant FGF21 was administrated in vivo and in vitro to determine its therapeutic effect.

Results

Serum FGF21 levels in patients and mice with VILI were significantly higher than in those without VILI. Additionally, the increment of serum FGF21 in anesthesia patients was positively correlated with the duration of ventilation. VILI was aggravated in FGF21-KO mice compared with WT mice. Conversely, the administration of FGF21 alleviated VILI in both mouse and cell models. FGF21 reduced Caspase-1 activity, suppressed the mRNA levels of Nlrp3, Asc, Il-1β, Il-18, Hmgb1 and Nf-κb, and decreased the protein levels of NLRP3, ASC, IL-1β, IL-18, HMGB1 and the cleaved form of GSDMD.

Conclusions

Our findings reveal that endogenous FGF21 signaling is triggered in response to VILI, which protects against VILI by inhibiting the NLRP3/Caspase-1/GSDMD pyroptosis pathway. These results suggest that boosting endogenous FGF21 or the administration of recombinant FGF21 could be promising therapeutic strategies for the treatment of VILI during anesthesia or critical care.