bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing Organizational Capacity to Advance Health Equity: Mixed-Methods Approach at a Local Health Department
Authors: Singh Shipra , Polavarapu Mounika , Vallerand Katharine , Bhoge Yashika , Noviski Krista McCarthy
Published: November 2023

Local health departments (LHDs) play a leading role in eliminating health inequities as they proactively identify and address barriers to optimal health within the community they serve. This study evaluated a Midwestern County LHD’s commitment, collaborations, and capacity to advance health equity in their organization. A total of 81 employees completed the online survey (response rate = 51%) and 12 among randomly selected employees completed the qualitative interviews (31.5%). More than 75% of participants reported that all departments had explicit work plans and 50% had a strong capacity to address social determinants of health. Almost 50% of the participants reported strong internal collaboration, but less than 25% indicated that no external partners were involved during the program planning process. Finally, a few participants identified the need for increased diversity in leadership and expressed the importance of quality training and feedback.
A Markov analysis of azacitidine and venetoclax vs induction chemotherapy for medically fit patients with AML
Authors: Ravindran Mithunan , Mozessohn Lee , Cheung Matthew , Buckstein Rena , Teichman Jennifer
Published: November 2023

Although induction chemotherapy (IC) is the standard of care in medically fit patients with newly diagnosed acute myeloid leukemia (AML), limited retrospective data indicate that patients at adverse-risk may benefit from azacytidine and venetoclax (aza-ven). Our goal was to perform a Markov decision analysis to determine whether IC or aza-ven is the optimal induction regimen in this population. Using the TreeAge software, Markov models were created for adverse-risk and intermediate-risk cohorts. A systematic review of the literature informed the transition probabilities and utilities included in the analyses. Our primary outcome was quality-adjusted life years (QALYs) gained over 5 years after diagnosis. Overall, patients at adverse risk treated with IC gained 1.4 QALYs, compared with 2.0 QALYs in patients treated with aza-ven. Patients at adverse risk treated with IC and allogeneic stem cell transplantation (allo-SCT), IC, aza-ven and allo-SCT, or aza-ven gained 2.1, 1.5, 3.0, and 1.9 QALYs, respectively. Meanwhile, patients at intermediate risk treated with IC gained 2.0 QALY, compared with 1.7 QALY in patients treated with aza-ven. Patients at intermediate risk treated with IC and allo-SCT, IC, aza-ven and allo-SCT, and aza-ven gained 2.7, 2.3, 2.6, and 1.8 QALYs, respectively. We have demonstrated that medically fit patients with newly diagnosed adverse-risk AML may benefit from treatment with aza-ven over those treated with IC, whereas IC remains the preferred approach for patients at intermediate risk. Our work challenges the use of the European LeukemiaNet risk classification for patients treated with aza-ven and highlights the need for prospective investigation into aza-ven as induction therapy for medically fit patients.
Recombinant erythropoietin in autoimmune hemolytic anemia with inadequate bone marrow response: a prospective analysis
Authors: Fattizzo Bruno , Pedone Giacinto Luca , Brambilla Caterina , Pettine Loredana , Zaninoni Anna , Passamonti Francesco , Barcellini Wilma
Published: November 2023

Up to 30% of patients with autoimmune hemolytic anemia (AIHA) show inadequate bone marrow (BM) compensatory response with inappropriately low levels of reticulocytes and endogenous erythropoietin. Ineffective BM compensation is associated with more severe anemia, transfusion need, and hospital admission, and treatment with recombinant erythropoietin (rEPO) may be beneficial. Here, we prospectively analyzed the efficacy and safety of rEPO in a single-center cohort of 47 patients with AIHA with inadequate reticulocytosis and endogenous erythropoietin at baseline. Epoetin alpha 40 000 international units per week were administered subcutaneously until hemoglobin (Hb) >11 g/dL and then tapered off. Overall response was 55% at 15 days, 74% at 1 month, 74% at 3 months, 80% at 6 months, and 91% at 12 months. Consistently, Hb values significantly increased from baseline to each subsequent time point (P<.001) with a median increase of +1.4, +2.4, +3.4, +3.8, and +4.4 g/dL, respectively. Transfusion needs reduced from 30% to <10% at 15 days and thereafter (P < .001). Concomitant medications included prednisone or methylprednisolone (N = 40, stable since >2 weeks from enrollment), mycophenolate mofetil (N = 1, ongoing since >3 months from enrollment), and rituximab (N = 7 patients with cold agglutinin disease from day 8). No association between concomitant medications and response to rEPO was found. Treatment was generally safe without rEPO-related severe adverse events. The comparison with an AIHA population not treated with rEPO showed a significant benefit of rEPO at 15 days and 1 month on response and Hb increase. These data support the use of rEPO as an add on to standard immunosuppression in AIHA with inadequate BM compensation. This trial was registered at www.clinicaltrials.gov as #NCT05931718.
Metagenomic analysis reveals distinct changes in the gut microbiome of obese Chinese children
Authors: Li Ping , Jiang Jiyang , Li Yifei , Lan Yue , Yang Fan , Wang Jiao , Xie Yuxin , Xiong Fei , Wu Jinhui , Liu Hanmin , Fan Zhenxin
Published: November 2023

Background

The prevalence of obese children in China is increasing, which poses a great challenge to public health. Gut microbes play an important role in human gut health, and changes in gut status are closely related to obesity. However, how gut microbes contribute to obesity in children remains unclear. In our study, we performed shotgun metagenomic sequencing of feces from 23 obese children, 8 overweight children and 22 control children in Chengdu, Sichuan, China.

Results

We observed a distinct difference in the gut microbiome of obese children and that of controls. Compared with the controls, bacterial pathogen Campylobacter rectus was significantly more abundant in obese children. In addition, functional annotation of microbial genes revealed that there might be gut inflammation in obese children. The guts of overweight children might belong to the transition state between obese and control children due to a gradient in relative abundance of differentially abundant species. Finally, we compared the gut metagenomes of obese Chinese children and obese Mexican children and found that Trichuris trichiura was significantly more abundant in the guts of obese Mexican children.

Conclusions

Our results contribute to understanding the changes in the species and function of intestinal microbes in obese Chinese children.
Detection of virulence genes of Staphylococcus aureus isolated from raw beef for retail sale in the markets of Ulaanbaatar city, Mongolia
Authors: Dorjgochoo Amgalanzaya , Batbayar Anujin , Tsend-Ayush Altansukh , Erdenebayar Otgontsetseg , Byambadorj Bayarlakh , Jav Sarantuya , Yandag Munkhdelger
Published: November 2023

Background

Staphylococcus aureus (S. aureus) is a highly virulent pathogen that causes food-borne illness, food poisoning, skin and soft tissue infections, abscesses, mastitis, and bacteremia. It is common for meat and meat products to become contaminated with S. aureus due to dirty hands, food storage conditions, food production processes, and unhygienic conditions, causing food poisoning. Therefore, we aimed to isolate S. aureus strain from the raw beef and reveal virulence genes and antibiotic resistance profile from isolated S. aureus strains.

Methods

In this study, 100 samples of raw beef were collected from 4 major market stalls in Ulaanbaatar city, Mongolia. S. aureus was detected according to the ISO 6888–1:2021 standard, and the nucA gene encoding the species-specific thermonuclease was amplified and confirmed by polymerase chain reaction (PCR). In the strains of S. aureus isolated from the samples, the genes encoding the virulence factors including sea, sed, tsst, eta, etb, and mecA were amplified by multiplex PCR. These genes are encoded staphylococcal enterotoxin A, enterotoxin D, toxic shock syndrome toxin, exotoxin A, exotoxin B and penicillin-binding protein PBP 2A, respectively. Antibiotic sensitivity test was performed by the Kirby–Bauer disc diffusion method. The Clinical and Laboratory Standard Institute guidelines as CLSI M100-S27 was used for analysis of the data.

Results

Thirty-five percent of our samples were detected contaminated with of the S. aureus strains. Subsequently, antibiotic resistance was observed in the S. aureus contaminated samples. Among our samples, the highest rates of resistance were determined against ampicillin (97.1%), oxacillin (88.6%), and penicillin (88.6%), respectively. Three genes including mecA, sea, and tsst from six virulence genes were detected in 17% of S. aureus strain-contaminated samples by multiplex PCR. The sed, etb and eta genes were detected in the 2.9%, 11.4% and 5.7% of our samples, respectively.

Conclusion

The results show that S. aureus related contamination is high in the raw beef for retail sale and prevalent S. aureus strains are resistant to all antibiotics used. Also, our results have demonstrated that there is a high risk for food poisoning caused by antibiotic resistant S. aureus in the raw beef and it may establish public health issues. Genes encoding for both heat-resistant and nonresistant toxicity factors were detected in the antibiotic resistant S. aureus strains and shown the highly pathogenic. Finally, our study is ensuring to need proper hygienic conditions during beef’s preparation and sale.
Deep Learning Approaches for Automatic Quality Assurance of Magnetic Resonance Images Using ACR Phantom
Authors: Torfeh Tarraf , Aouadi Souha , Yoganathan SA , Paloor Satheesh , Hammoud Rabih , Al-Hammadi Noora
Published: November 2023

Background

In recent years, there has been a growing trend towards utilizing Artificial Intelligence (AI) and machine learning techniques in medical imaging, including for the purpose of automating quality assurance. In this research, we aimed to develop and evaluate various deep learning-based approaches for automatic quality assurance of Magnetic Resonance (MR) images using the American College of Radiology (ACR) standards.

Methods

The study involved the development, optimization, and testing of custom convolutional neural network (CNN) models. Additionally, popular pre-trained models such as VGG16, VGG19, ResNet50, InceptionV3, EfficientNetB0, and EfficientNetB5 were trained and tested. The use of pre-trained models, particularly those trained on the ImageNet dataset, for transfer learning was also explored. Two-class classification models were employed for assessing spatial resolution and geometric distortion, while an approach classifying the image into 10 classes representing the number of visible spokes was used for the low contrast.

Results

Our results showed that deep learning-based methods can be effectively used for MR image quality assurance and can improve the performance of these models. The low contrast test was one of the most challenging tests within the ACR phantom.

Conclusions

Overall, for geometric distortion and spatial resolution, all of the deep learning models tested produced prediction accuracy of 80% or higher. The study also revealed that training the models from scratch performed slightly better compared to transfer learning. For the low contrast, our investigation emphasized the adaptability and potential of deep learning models. The custom CNN models excelled in predicting the number of visible spokes, achieving commendable accuracy, recall, precision, and F1 scores.
Health and wellbeing outcomes associated with loneliness for people with disability: a scoping review
Authors: Bailie Jodie , Bishop Glenda M. , Badland Hannah , Emerson Eric , Aitken Zoe , Stancliffe Roger , Ekanayake Kanchana , Llewellyn Gwynnyth
Published: November 2023

Background

Loneliness is a significant public health concern due to its detrimental impact on health and wellbeing. Despite people with disability reporting higher levels of loneliness than the general population, there has been little research into how this is affecting their health and wellbeing. In light of this, the aim of our study was to scope both the existing evidence about the health and wellbeing outcomes associated with loneliness for people with disability, as well as the conceptual frameworks and measures utilised in this field of research.

Methods

To conduct this scoping review, we followed the methodology outlined by JBI and searched MEDLINE, Scopus, Informit, Embase, and Web of Science for peer-reviewed, English-language articles published between 1 January 2000 and 8 February 2023. Two independent reviewers completed screening, full-text review and data extraction, with consensus sought at each stage. Data were analysed using content analysis and presented both numerically and narratively.

Results

Out of the initial 1602 publications identified in the scoping review, only nine were included after duplicate removal, title and abstract screening, and full-text review. This limited number of studies, with the earliest study one published in 2015, represents a key finding. Eight of the nine studies were quantitative, and all were conducted in high income countries. Most of these studies utilised a version of the University of Los Angles Loneliness Scale to measure loneliness and addressed specific impairment groups. Notably, most of the studies identified associations between loneliness and health and wellbeing outcomes for people with disability.

Conclusions

This scoping review highlights the current scarcity of studies examining the effect that loneliness has on the health and wellbeing outcomes of people with disability. As most of the reviewed studies relied on loneliness measures designed for individuals without disability, they potentially overlook the unique life experiences of people with disability. Given that loneliness is an international public health concern, it is imperative that people with disability are not left behind or overlooked in efforts to address the impact of loneliness on health and wellbeing.
Quality of life and factors associated among caregivers of adolescent and young adult Ebola survivors in Democratic Republic of the Congo, a cross-sectional study
Authors: Munyumu Kisughu , Wafula Charles , Were Vincent , Katungu Françoise , Mbasa Ndemo , Kaseje Margaret
Published: November 2023

Background

Ebola virus disease is a medical condition whose consequent effects on quality of life of patients. In the history of infectious diseases, there have been pathologies that have had significant repercussions for caregivers, healthcare providers and the community.

Objectives

This study investigate determinants of quality of life among caregivers of adolescent and young adult Ebola survivors in Democratic Republic of the Congo.

Methods

This was a cross sectional study. The study sites were the two health districts of Beni and Katwa, in North-Kivu province in the Eastern part of Democratic Republic of the Congo. The study period was from April to August 2022. Participants of the study were caregivers of adolescents and young adult Ebola virus survivors. Simple random sampling technique was used to select the 68 study participants. A questionnaire was administered. Data was collected using pretested questionnaire of WHO quality of life Bref (WHOQOL-BREF) and CommCare by Dimagi.Inc. lastest Version 2.52.1 and  a sum of score of 78 or higher indicated a high level of life quality. To determine the quality of life of caregivers of adolescents and young adult EVD survivors, descriptive analysis was used. The Pearson correlation coefficient was utilized to check whether the predictor variables are multicollinear. The regression analysis produced the crude odds ratio (COR), adjusted odds ratio (aOR), 95% confidence interval (CI), and p-value. Statistical significance was defined as a p-value 0.05. The final multivariate model contained variables that were significant in the bivariate analysis. Prior to data collection, a research permit from National Ethical Committee of Research in Democratic Republic of the Congo was obtained. Written informed consents from literate or illiterate caregivers of adolescent and young adult Ebola survivors were obtained. Throughout the study, participants' privacy and confidentiality were respected.

Results

A total of 68 care givers participated in the study, with a majority 54/68(79.41%) having poor quality of life. Men were 3.17 times more likely to record good quality of life than women (p = 0.02); OR:(95% CI), 3.17: (1.2 – 8.36), With regards to place of residence, caregivers who lived in town were less likely to have good quality of life compared to those in rural (p = 0.01); OR: (95%CI), 0.25: (0.09 – 0.72).

Conclusion

The quality of life of caregivers of adolescent and young adult Ebola survivors in Democratic Republic of the Congo is poor. To be woman caregiver and to live in town are determinants associated with poor quality of life among caregivers of adolescent and young adult Ebola survivors.
The burden of HEV-related acute liver failure in Bangladesh, China and India: a systematic review and meta-analysis
Authors: Dong Rui , Chang Dongchun , Luo Zhenghan , Zhang Mengting , Guan Qing , Shen Chao , Chen Yue , Huang Peng , Wang Jie
Published: November 2023

Background

Hepatitis E can potentially progress to HEV-related acute liver failure (HEV-ALF). East and South Asia bear a substantial burden of HEV infection, with Bangladesh, China, and India facing the most severe threat in this region. Therefore, we conducted a systematic review and meta-analysis to evaluate the burden of HEV-ALF in these three high-risk countries.

Methods

A systematic literature search was performed utilizing PubMed, the Cochrane Library, Medline, Embase, and Web of Science databases. Studies in English or Chinese that reported data on the burden of HEV-ALF in Bangladesh, China and India were included. Outcomes were pooled with meta-analysis utilizing R software. Estimates were calculated with random-effects models, and subgroup analysis and sensitivity analysis were conducted to address heterogeneity. Egger’s test and Begg’s test were performed to assess publication bias.

Results

A total of 20 eligible studies were included in this study. The pooled HEV-attributable proportion of viral-related acute liver failure was estimated to be 40.0% (95% CI: 0.28–0.52), 30.0% (95% CI: 0.18–0.44), and 61.0% (95% CI: 0.49–0.72) among non-pregnant individuals in India, China and Bangladesh, while in Indian pregnant females, it was 71.0% (95% CI: 0.62–0.79). The combined prevalence among non-pregnant HEV-infected participants was 28.0% (95% CI: 0.20–0.37) and 10.0% (95% CI: 0.01–0.28) in India and China, and it was 34.0% (95% CI: 0.27–0.42) in Indian pregnant females with HEV infection. The overall mortality of HEV-ALF was estimated to be 32.0% (95% CI: 0.23–0.42) and 64.0% (95% CI: 0.50–0.77) among the non-pregnant and the pregnant participants in India, and it was 23.0% (95% CI: 0.14–0.34) in Chinese non-pregnant participants.

Conclusions

The burden of HEV-ALF in Bangladesh, China, and India is non-negligible despite geographic and population heterogeneity. The prevention of HEV infection and early recognition of HEV-ALF are of great significance, especially in high-risk countries and populations.

Registration

PROSPERO registration ID is CRD42022382101.
The predictive value of baseline symptom score and the peripheral CD4CD8 double-positive T cells in patients with AECOPD
Authors: He Shiyi , Wu Shiyu , Chen Tianwei , Huang Weina , Yu Aiping , Cao Chao
Published: November 2023

Background

Accurate prediction of acute exacerbation helps select patients with chronic obstructive pulmonary disease (COPD) for individualized therapy. The potential of lymphocyte subsets to function as clinical predictive factors for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) remains uncertain.

Methods

In this single-center prospective cohort study with a 2-year follow-up, 137 patients aged 51 to 79 with AECOPD were enrolled. We examined the prognostic indicators of AECOPD by analyzing lymphocyte subsets and baseline symptom score. Furthermore, a predictive model was constructed to anticipate the occurrence of respiratory failure in patients experiencing AECOPD.

Results

The COPD Assessment Test (CAT) score combined with home oxygen therapy and CD4+CD8+ T cells% to predict respiratory failure in AECOPD patients were the best (the area under the curves [AUC] = 0.77, 95% CI: 0.70–0.86, P < 0.0001, sensitivity: 60.4%, specificity: 86.8%). The nomogram model, the C index, calibration plot, decision curve analysis, and clinical impact curve all indicate the model’s good predictive performance. The observed decrease in the proportions of CD4+CD8+ T cells appears to be correlated with more unfavorable outcomes.

Conclusions

The nomogram model, developed to forecast respiratory failure in patients with AECOPD, utilizing variables such as home oxygen therapy, CAT score, and CD4+CD8+ T cells%, demonstrated a high level of practicality in clinical settings. CD4+CD8+ T cells serve as a reliable and readily accessible predictor of AECOPD, exhibiting greater stability compared to other indices. It is less susceptible to subjective influences from patients or physicians. This model facilitated personalized estimations, enabling healthcare professionals to make informed decisions regarding preventive interventions.
Efficacy of N-acetylcysteine plus pirfenidone in the treatment of idiopathic pulmonary fibrosis: a systematic review and meta-analysis
Authors: Zhang Xiu-Li , Cao Ying , Zheng Bo
Published: November 2023

Background

Numerous studies have demonstrated the potential of pirfenidone to enhance the prognosis of patients afflicted with idiopathic pulmonary fibrosis (IPF). Although N-acetylcysteine (NAC) is utilized as an antioxidant in IPF treatment, the combination of NAC and pirfenidone has produced inconsistent outcomes in certain studies. To assess the clinical effectiveness and safety of NAC plus pirfenidone (designated as the treatment group) versus pirfenidone monotherapy (designated as the control group), we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs).

Methods

RCTs of NAC plus pirfenidone were reviewed searching from databases and networks of unpublished and published studies in any language. Using pair-wise meta-analysis, changes in pulmonary function test (PFT) parameters and safety were evaluated.

Results

Two independent reviewers selected and obtained data from 5 RCTs (n = 398), comprising 1 study from Japan, 1 from Europe, and 3 from China. NAS plus pirfenidone as compared to pirfenidone monotherapy for IPF may not reduce the incidence of skin effects(RR 1.26 [95%CI 0.64 to 2.45]) and mortality(RR 0.35 [95%CI 0.07 to 1.68])(both moderate certainty). NAS plus pirfenidone as compared to pirfenidone monotherapy for IPF may not reduce the incidence of at least one side effects(RR 1.00 [95%CI 0.84 to 1.19]; low certainty),severe side effects(RR 0.67 [95%CI 0.30 to 1.47]; low certainty) and gastrointestinal effects(RR 0.67 [95%CI 0.41 to 1.09]; low certainty) with possibly no effect in Δ%DLco(SMD -0.17 [95%CI -0.15 to 0.48]; low certainty). Meanwhile, the effect of NAS plus pirfenidone as compared to pirfenidone monotherapy on ΔFVC(SMD 0.18 [95%CI -0.68 to 1.05]), Δ%FVC(SMD -2.62 [95%CI -5.82 to 0.59]) and Δ6MWT(SMD -0.35 [95%CI -0.98 to 0.28]) is uncertain(extremely low certainty).

Conclusion

Moderate certainty evidence suggests that NAS plus pirfenidone, compared to pirfenidone monotherapy for IPF, does not reduce the incidence of skin effects and mortality.
Elucidating the role of RBM5 in osteoclastogenesis: a novel potential therapeutic target for osteoporosis
Authors: Zhang Yuyang , Chen Xue , Xiao Yuan , Mei Yibo , Yang Tong , Li Dongchen , Wang Xiaohui , Yang Hao , Huang Dageng , Hao Dingjun
Published: November 2023

Osteoporosis is a prevalent bone disease with multigene involved, and the molecular mechanisms of its pathogenesis are not entirely understood. This study aims to identify novel key genes involved in osteoporosis to discover potential pharmacological targets. We analyzed three microarray datasets and identified four differentially expressed genes. The LASSO model indicated that RNA-binding motif protein 5 (RBM5) is associated with osteoporosis and is a potential drug target. We conducted the Spearman correlation analysis and found 52 genes that were significantly related to RBM5. Enrichment analysis showed that these genes were primarily involved in RNA splicing and osteoclast differentiation pathways. By using lentivirus-based shRNA, we successfully knocked down RBM5 expression in RAW264.7 cell line, which showed that RBM5 knockdown significantly impaired their differentiation potential to mature osteoclasts and significantly inhibited bone-resorbing activity. RT-qPCR analyses revealed the expression of osteoclastogenesis marker genes was downregulated along with RBM5 expression. These findings suggest that RBM5 plays a crucial role in the pathogenesis of osteoporosis and provides a new potential pharmacological target.
What is the safe and effective dilator number during access in PCNL? Three-shot dilation versus classical sequential Amplatz dilation
Authors: Memik Omur , Voyvoda Bekir , Ustuner Murat , Karsli Onur , Halat Ahmed Omer , Ozcan Levent
Published: November 2023

Background

Although PCNL has been used for a long time to treat nephrolithiasis, there is still contradictory information concerning the use of the dilation method. In this study, we aimed to compare conventional sequential Amplatz dilatation (SAD) using ten dilators and a method using three dilators (12, 20, and 30 Fr), which we named “three-shot dilatation” (3SD), in terms of fluoroscopy time (FT), operation time, bleeding and stone-free rates.

Methods

The study included patients who underwent PCNL with the SAD and 3SD methods. A different surgeon with extensive endourology experience applied each technique. One of the surgeons operated on the patients using the SAD method with ten dilators, and the other surgeon performed the operations using the 3SD method involving three Amplatz dilators (12, 20, and 30 Fr).

Results

A total of 283 patients, 138 in the 3SD group and 145 in the SAD group, were included in the study. The mean age of the patients was 47.32 ± 13.71 years. There was no statistically significant difference between the two groups regarding preoperative characteristics (p > 0.05). The FTs of access 2, total access, and total operation were significantly shorter in the 3SD group (p = 0.0001). The decrease in hemoglobin was statistically significant in the 3SD group compared to the SAD group (p = 0.022), while the blood transfusion requirements of the groups were similar (p = 0.176). There was no statistically significant difference between the two groups regarding stone-free rates (p = 0.973). In four patients in the SAD group, re-access was necessary due to the loss of passage due to the guide wire slipping out of its place.

Conclusion

Intraoperative FT can be shortened using the described 3SD method without compromising surgical safety. However, this method can be used as an intermediate step in the transition to one-shot dilation by surgeons experienced in performing SAD.
Bilateral co-secretory lesions presenting with coexisting Cushing syndrome and primary aldosteronism: a case report
Authors: Gao Hongjiao , Li Li , Chen Fei , Ren Yan , Chen Tao , Tian Haoming
Published: November 2023

Background

There is an increasing number of cases of aldosterone- and cortisol-producing adenomas (A/CPAs) reported in the context of primary aldosteronism (PA). Most of these patients have PA complicated with subclinical Cushing's syndrome; cases of apparent Cushing's syndrome (CS) complicated with aldosteronism are less reported. However, Co-secretory tumors were present in the right adrenal gland, a cortisol-secreting adenoma and an aldosterone-producing nodule (APN) were present in the left adrenal gland, and aldosterone-producing micronodules (APMs) were present in both adrenal glands, which has not been reported. Here, we report such a case, offering profound insight into the diversity of clinical and pathological features of this disease.

Case presentation

The case was a 45-year-old female from the adrenal disease diagnosis and treatment centre in West China Hospital of Sichuan University. The patient presented with hypertension, moon-shaped face, central obesity, fat accumulation on the back of the neck, disappearance of cortisol circadian rhythm, ACTH < 5 ng/L, failed elevated cortisol inhibition by dexamethasone, orthostatic aldosterone/renin activity > 30 (ng/dL)/(ng/mL/h), and plasma aldosterone concentration > 10 ng/dL after saline infusion testing. Based on the above, she was diagnosed with non-ACTH-dependent CS complicated with PA. Adrenal vein sampling showed no lateralization for cortisol and aldosterone secretion in the bilateral adrenal glands. The left adrenocortical adenoma was removed by robot-assisted laparoscopic resection. However, hypertension, fatigue and weight gain were not alleviated after surgery; additionally, purple striae appeared in the lower abdomen, groin area and inner thigh, accompanied by systemic joint pain. One month later, the right adrenocortical adenoma was also removed. CYP11B1 were expressed in the bilateral adrenocortical adenomas, and CYP11B2 was also expressed in the right adrenocortical adenomas. APN existed in the left adrenal gland and APMs in the adrenal cortex adjacent to bilateral adrenocortical adenomas. After another surgery, her serum cortisol and plasma aldosterone returned to normal ranges, except for slightly higher ACTH.

Conclusions

This case suggests that it is necessary to assess the presence of PA, even in CS with apparent symptoms. As patients with CS and PA may have more complicated adrenal lesions, more data are required for diagnosis.
Accuracy of fit for cobaltchromium bar over two implants fabricated with different manufacturing techniques: an in-vitro study
Authors: Nassar Hossam I. , Fateen Ayman
Published: November 2023

Objective

The purpose of the invitro research was to compare the fit of Cobalt Chromium customized bar fabricated with different manufacturing processes cast metal bar, milled bar and 3D printed bar using scanning electron microscope.

Materials and methods

Clear epoxy resin molds were prepared. In each mold two parallel implants with a 14 mm distance from each other were embedded. Thirty Co-Cr custom bars were constructed and were divided equally into three groups: Group (I) (Co-Cr conv), group (II) milled bar (Co-Cr milled), and group (III) printed bar (Co-Cr print). The marginal fit at implant-abutment interface was scanned using scanning electron microscope (SEM).

Results

There was a significant difference between the three studied groups regarding marginal misfit the between implant and fabricated bars with p-value < 0.001. The highest value of micro-gap distance was found in Co-Cr conventional group (7.95 ± 2.21 μm) followed by Co-Cr 3D printed group (4.98 ± 1.73) and the lower value were found in Co-Cr milled (3.22 ± 0.75).

Conclusion

The marginal fit of milled, 3D printed and conventional cast for Co-Cr alloy were within the clinically acceptable range of misfit. CAD/CAM milled Co-Cr bar revealed a superior internal fit at the implant-abutment interface. This was followed by selective laser melting (SLM) 3D printed bar and the least fit was shown for customized bar with the conventional lost wax technique.
The need for hands-on training and supervision for entry-level physicians in a country with low surgical staffing density: a nationwide survey in Ghana
Authors: Kang Mee Joo , Kwesi Sakyi Ngissah Reuben , Bo-Ib Buunaaim Alexis Dun , Baidoo Richard , Odei-Ansong Francis , Wordui Theodore , Adjepong-Tandoh Ernest Kwame , Baidoo Paa Kwesi , Aggrey-Orleans James Emmanuel Kwegyir
Published: November 2023

Background

Despite the largely unmet need, relatively few medical school graduates enrol in surgical residency and fewer surgical specialists work rurally in low- and middle-income countries. Surgical housemanship is the only formal training for medical graduates who will become the main surgical care providers in underserved areas. This study aimed to evaluate Ghanaian surgical housemanship (internship) and its impact on independent medical practice.

Methods

A nationwide questionnaire survey of surgical trainees from seven teaching or regional-level hospitals ascertained the experience and self-confidence levels for 35 training objectives set by the Medical and Dental Council of Ghana, and suggestions to improve surgical training quality.

Results

Of 310 respondents, 59.7% experienced ≤ 10 cases for each topic, and 24.8% reported self-confidence as ≤ 2 points (out of 5). More than 90% of respondents experienced ≤ 10 cases for gastric, colorectal and liver cancer management. Teaching hospital trainees had lower proportions of those experiencing > 10 cases (36.6% versus 43.7%) and reporting self-confidence ≥ 4 (46.5% versus 55.8%), respectively, compared with those from regional/other-level hospitals. 40% of respondents were not confident about their surgical skills, and 70.5% requested better-supervised and practical surgical skills training. The proportion of respondents who reported limited supervision was higher among those from teaching hospitals, reported self-confidence scores < 4, and experienced ≤ 10 cases for each topic. 67% of respondents were satisfied with their surgical housemanship and 75.8% perceived surgical rotation as relevant to their future work.

Conclusions

Most surgical trainees are concerned about their surgical skills. A structured curriculum with specific goals and better-supervised surgical skills training should be established. Inclusion of regional/other-level hospitals in surgical training may reduce the supervisory burden in teaching hospitals.
Therapeutical strategies in cavitary legionnaires’ disease, two cases from the field and a systematic review
Authors: Moretti Marco , De Boek Lisanne , Ilsen Bart , Demuyser Thomas , Vanderhelst Eef
Published: November 2023

Background

Legionnaires’ Disease (LD) rarely evolves into pulmonary abscesses. The current systematic review has been designed to explore therapeutical strategies in pulmonary cavitary LD.

Methods

A research strategy was developed and applied to the databases Embase, Pubmed, and Web of Science from the 1st of January 2000 to the 1st of November 2022. Original articles, case series, case reports, and guidelines written in English, French, German, Italian, and Dutch were considered. Furthermore, medical records of patients treated at the University Hospital UZ Brussel for LD cavitary pneumonia, between the 1st of January 2016 to the 1st of January 2022, were reviewed.

Results

Two patients were found by the UZ Brussel’s medical records investigation. Through the literature review, 23 reports describing 29 patients, and seven guidelines were identified. The overall evidence level was low.

Result of synthesis (case reports)

The median age was 48 years and 65% were male. A polymicrobial infection was detected in 11 patients (44%) with other aerobic bacteria being the most commonly found. At diagnosis, 52% of patients received combination therapy, and fluoroquinolones were the preferred antimicrobial class. Anaerobic coverage was neglected in 33% of patients.

Result of synthesis (guidelines)

Three guidelines favor monotherapy with fluoroquinolones or macrolides, while one suggested an antimicrobial combination in case of severe LD. Four guidelines recommended anaerobic coverage in case of lung abscesses.

Conclusion

To date, the evidence supporting cavitary LD treatment is low. Monotherapy lowers toxicity and might be as effective as combination therapy. Finally, anaerobes should not be neglected.

Graphical Abstract
Porcine promyelocytic leukemia protein isoforms suppress Japanese encephalitis virus replication in PK15 cells
Authors: Chen Zhenyu , Liu Huaijin , Zhu Jingjing , Duan Xing , Wang Han , Li Xiangchen , Zhou Xiaolong , Zhao Ayong , Yang Songbai
Published: November 2023

Background

Promyelocytic leukemia protein (PML) is a primary component of PML nuclear bodies (PML-NBs). PML and PML-NBs play critical roles in processes like the cell cycle, DNA damage repair, apoptosis, and the antiviral immune response. Previously, we identified five porcine PML alternative splicing variants and observed an increase in the expression of these PML isoforms following Japanese encephalitis virus (JEV) infection. In this study, we examined the functional roles of these PML isoforms in JEV infection.

Methods

PML isoforms were either knocked down or overexpressed in PK15 cells, after which they were infected with JEV. Subsequently, we analyzed the gene expression of PML isoforms, JEV, and the interferon (IFN)-β signaling pathway using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. Viral titers were determined through 50% tissue culture infectious dose (TCID50) assays.

Results

Our results demonstrated that the knockdown of endogenous PML promoted JEV replication, while the overexpression of PML isoforms 1, 3, 4, and 5 (PML1, PML3, PML4, and PML5) inhibited JEV replication. Further investigation revealed that PML1, PML3, PML4, and PML5 negatively regulated the expression of genes involved in the interferon (IFN)-β signaling pathway by inhibiting IFN regulatory factor 3 (IRF3) post-JEV infection.

Conclusions

These findings demonstrate that porcine PML isoforms PML1, PML3, PML4, and PML5 negatively regulate IFN-β and suppress viral replication during JEV infection. The results of this study provide insight into the functional roles of porcine PML isoforms in JEV infection and the regulation of the innate immune response.
Association between co-infection with Chlamydia trachomatis or Mycoplasma genitalium and cervical lesions in HPV-positive population in Hunan, China: a cross-sectional study
Authors: Jiang Mengjie , Ding Hui , He Ling , Xu Danning , Jiang Ping , Tang Haoneng , Wang Qian , Wang Xuemei , Tang Lingli
Published: November 2023

Objectives

The aim of this study was to determine the prevalence of Chlamydia trachomatis (CT) and Mycoplasma genitalium (MG) among HPV-positive women undergoing colposcopy at the Second Xiangya Hospital of Central South University, Hunan, China. Additionally, we aimed to assess the impact of C. trachomatis or M. genitalium co-infection with HPV on the severity of cervical lesions.

Methods

We collected HPV data, cervical cytology results, and demographic information from 439 women attending colposcopy. Cervical swabs were obtained for simultaneous amplification testing (SAT) of C. trachomatis and M. genitalium. Multivariate logistic regression analyses were performed to examine the association between sexually transmitted pathogens and cervical lesions.

Results

Among the participants, C. trachomatis was detected in 17 (3.87%) individuals, and M. genitalium in 16 (3.64%) individuals. There was no co-infection of C. trachomatis and M. genitalium. The highest prevalence of M. genitalium was observed in women aged 19–30 years (10.20%; 95% CI, 1.41-18.99%), with a subsequent decline in prevalence with increasing age (Ptrend = 0.014). The most common HPV subtype in our study was HPV52 (30.79%), followed by HPV16 (18.62%), HPV58 (16.95%), and HPV53 (10.02%). Infection with HPV16 (OR = 3.43, 95% CI, 2.13–5.53), HPV31 (OR = 3.70, 95% CI, 1.44–9.50), and HPV33 (OR = 3.71, 95% CI, 1.43–9.67) was associated with an increased severity of cervical lesions, while HPV53 infection was not likely to lead to advanced cervical lesions (OR = 0.45, 95% CI, 0.23–0.89). The leukocyte level in vaginal secretions (P = 0.042) and cervical cytology results (P < 0.001) showed associations with the degree of cervical lesions. However, there was no significant association between C. trachomatis or M. genitalium infection and the severity of cervical lesions, nor with their co-infection with HPV16.

Conclusions

There was no correlation between co-infection of Chlamydia trachomatis or Mycoplasma genitalium and the degree of cervical lesions in HPV-positive population in Hunan, China. Our findings emphasized the need to pay more attention to M. genitalium infection among young women. Increased levels of leukocytes in vaginal secretions may be linked to cervical lesions. HPV16, HPV31, and HPV33 in Hunan province, China, may exhibit higher cervical pathogenicity.
Imp is expressed in INPs and newborn neurons where it regulates neuropil targeting in the central complex
Authors: Munroe Jordan A. , Doe Chris Q.
Published: November 2023

The generation of neuronal diversity remains incompletely understood. In Drosophila, the central brain is populated by neural stem cells derived from progenitors called neuroblasts (NBs). There are two types of NBs, type 1 and 2. T1NBs have a relatively simple lineage, whereas T2NBs expand and diversify the neural population with the generation of intermediate neural progenitors (INPs), contributing many neurons to the adult central complex, a brain region essential for navigation. However, it is not fully understood how neural diversity is created in T2NB and INP lineages. Imp, an RNA-binding protein, is expressed in T2NBs in a high-to-low temporal gradient, while the RNA-binding protein Syncrip forms an opposing gradient. It remains unknown if Imp expression is carried into INPs; whether it forms a gradient similar to NBs; and whether INP expression of Imp is required for generating neuronal identity or morphology. Here, we show that Imp/Syp are both present in INPs, but not always in opposing gradients. We find that newborn INPs adopt their Imp/Syp levels from their parental T2NBs; that Imp and Syp are expressed in stage-specific high-to-low gradients in INPs. In addition, there is a late INP pulse of Imp. We find that neurons born from old INPs (E-PG and PF-R neurons) have altered morphology following both Imp knock-down and Imp overexpression. We conclude that Imp functions in INPs and newborn neurons to determine proper neuronal morphology and central complex neuropil organization.
The effect of TLR3 priming conditions on MSC immunosuppressive properties
Authors: Tolstova Tatiana , Dotsenko Ekaterina , Kozhin Peter , Novikova Svetlana , Zgoda Victor , Rusanov Alexander , Luzgina Nataliya
Published: November 2023

Background

Mesenchymal stromal cells (MSCs) have regenerative and immunomodulatory properties, making them suitable for cell therapy. Toll-like receptors (TLRs) in MSCs respond to viral load by secreting immunosuppressive or proinflammatory molecules. The expression of anti-inflammatory molecules in MSCs can be altered by the concentration and duration of exposure to the TLR3 ligand polyinosinic-polycytidylic acid (poly(I:C)). This study aimed to optimize the preconditioning of MSCs with poly(I:C) to increase immunosuppressive effects and to identify MSCs with activated TLR3 (prMSCs).

Methods

Flow cytometry and histochemical staining were used to analyze MSCs for immunophenotype and differentiation potential. MSCs were exposed to poly(I:C) at 1 and 10 μg/mL for 1, 3, and 24 h, followed by determination of the expression of IDO1, WARS1, PD-L1, TSG-6, and PTGES2 and PGE2 secretion. MSCs and prMSCs were cocultured with intact (J−) and activated (J+) Jurkat T cells. The proportion of proliferating and apoptotic J+ and J− cells, IL-10 secretion, and IL-2 production after cocultivation with MSCs and prMSCs were measured. Liquid chromatography–mass spectrometry and bioinformatics analysis identified proteins linked to TLR3 activation in MSCs.

Results

Poly(I:C) at 10 μg/mL during a 3-h incubation caused the highest expression of immunosuppression markers in MSCs. Activation of prMSCs caused a 18% decrease in proliferation and a one-third increase in apoptotic J+ cells compared to intact MSCs. Cocultures of prMSCs and Jurkat cells had increased IL-10 and decreased IL-2 in the conditioned medium. A proteomic study of MSCs and prMSCs identified 53 proteins with altered expression. Filtering the dataset with Gene Ontology and Reactome Pathway revealed that poly(I:C)-induced proteins activate the antiviral response. Protein‒protein interactions by String in prMSCs revealed that the antiviral response and IFN I signaling circuits were more active than in native MSCs. prMSCs expressed more cell adhesion proteins (ICAM-I and Galectin-3), PARP14, PSMB8, USP18, and GBP4, which may explain their anti-inflammatory effects on Jurkat cells.

Conclusions

TLR3 activation in MSCs is dependent on exposure time and poly(I:C) concentration. The maximum expression of immunosuppressive molecules was observed with 10 µg/mL poly(I:C) for 3-h preconditioning. This priming protocol for MSCs enhances the immunosuppressive effects of prMSCs on T cells.
Single-cell analysis unveils activation of mast cells in colorectal cancer microenvironment
Authors: Xie Zhenyu , Niu Liaoran , Zheng Gaozan , Du Kunli , Dai Songchen , Li Ruikai , Dan Hanjun , Duan Lili , Wu Hongze , Ren Guangming , Dou Xinyu , Feng Fan , Zhang Jian , Zheng Jianyong
Published: November 2023

The role of mast cells (MCs) in colorectal cancer (CRC) remains unclear, and a comprehensive single-cell study on CRC MCs has not been conducted. This study used a multi-omics approach, integrating single-cell sequencing, spatial transcriptomics, and bulk tissue sequencing data to investigate the heterogeneity and impact of MCs in CRC. Five MC signature genes (TPSAB1, TPSB2, CPA3, HPGDS, and MS4A2) were identified, and their average expression was used as a marker of MCs. The MC density was found to be lower in CRC compared to normal tissue, but MCs in CRC demonstrated distinct activation features. Activated MCs were defined by high expression of receptors and MC mediators, while resting MCs had low expression. Most genes, including the five MC signature genes, were expressed at higher levels in activated MCs. The MC signature was linked to a better prognosis in both CRC and pan-cancer patient cohorts. Elevated KITLG expression was observed in fibroblasts and endothelial cells in CRC samples compared to normal tissue, and co-localization of MCs with these cell types was revealed by spatial transcriptome analysis. In conclusion, this study finds decreased MC density in CRC compared to normal tissue, but highlights a shift in MC phenotype from CMA1high resting cells to activated TPSAB1high, CPA3high, and KIThigh cells. The elevated KITLG expression in the tumor microenvironment’s fibroblasts and endothelial cells may activate MCs through the KITLG-KIT axis, potentially suppressing tumor progression.